Chitosan and its derivatives: From tailored synthesis to multifaceted bioactivities and transformative applications in the food industry – a review

Abstract

Chitosan is a versatile biopolymer produced by deacetylation of chitin. Structurally, it features reactive amino and hydroxyl groups and is primarily constituted of glucosamine units connected via β-(1,4)-glycosidic linkages. Chitosan and its derivatives not only exhibit unique physiological properties, such as excellent biocompatibility and biodegradability, but also demonstrate an array of notable biological activities, including immunomodulatory, antioxidative, hepatoprotective, anti-inflammatory, and antibacterial effects. Owing to their beneficial functional properties, chitosan and its derivatives have been extensively employed as immunomodulators, antimicrobial agents, and nutrient ingredients in various industrial and biomedical contexts. This review presents a comprehensive overview of current advances in the utilization of chitosan and its derivatives as health foods and biomaterials, with a focus on their preparation methods, biological activities, mechanisms of action, and practical applications. This systematic summary of chitosan and its derivatives paves the way for promising applications in the field of food nutrition and the food industry.

Highlights

• •Chitosan and its derivatives exhibit multifaceted bioactivities.
• •This review outlines the efficacy and application of chitosan and its derivatives.
• •Chitosan and its derivatives offer promising prospects for use in the food industry.

1. Introduction

Chitin is the second largest biomass resource in nature, and it is mainly derived from the shells of marine crustaceans such as crabs and shrimps, as well as insect exoskeletons, mollusk cartilages, and fungal cell walls (Khayrova, Lopatin, & Varlamov, 2021). The monomeric building unit of chitin is N-acetylglucosamine. Subjecting this unit to deacetylation yields chitosan (CS), which is a polymer chiefly composed of glucosamine residues. As an environmentally friendly renewable natural polymer material, chitosan is classified into α, β, and γ conformations. Its molecular structure comprises three key reactive sites: one amino group at the C₂ position, and two hydroxyl groups at the C₃ and C₆ positions, respectively (Gao, Tang, & Zhu, 2024). The presence of protonatable amino groups confers upon chitosan a unique cationic nature, distinguishing it as the only cationic polysaccharide found in nature. The density of these amino groups is directly proportional to the polymer's degree of deacetylation (DD) (Mohite et al., 2023). The molecular weight (MW) range of chitosan is usually from tens to thousands of kilo Dalton. The high MW of chitosan leads to its low water solubility and bioavailability.

Chitosan oligosaccharides (COS), also known as chitooligosaccharides and oligochitosan, are oligomers derived from the degradation of chitosan. The MW of COS is typically below 3900 Da, with a degree of polymerization (DP) ranging from 2 to 20 and a DD exceeding 90% (Leal et al., 2025). However, in some instances, molecules with an MW greater than 3900 Da and a DP higher than 20 have also been classified as COS rather than chitosan (Fang, Cong, Zhou, Zhang, & Wang, 2024). The relationship among chitin, chitosan, and COS is illuminated in Supplementary Fig. 1. Due to its low MW and high DD, COS exhibits superior water solubility and an enhanced ability to interact with cells, which directly contributes to its potent biological functions, such as antioxidative, immunomodulatory, anti-inflammatory, hepatoprotective, and antibacterial effects (Yuan et al., 2019).

The presence of reactive amino and hydroxyl groups at the C₂, C₃, and C₆ positions in both chitosan and COS makes them susceptible to chemical modification (Meivelu, 2025). Through the substitution of functional groups at their active sites, chitosan and COS can be modified to yield various derivatives with enhanced biological activities (Yang, Lan, & Sun, 2023). Common modifications of chitosan and COS encompass acylation, metal chelation, hydroxylation, cross-linking, esterification, and grafting (Yu et al., 2025). Due to their non-toxic nature, chitosan and its derivatives are widely applied in various fields, including biomedical materials (Manna et al., 2023), food industry (Onumah, Afoakwah, Boamah, Osei, & Amotoe-Bondzie, 2025), medicine (Cohen & Poverenov, 2022), and human nutrition (Yoo, Jung, Kwak, & Kim, 2024). Especially in the field of the food industry, chitosan and its derivatives are considered as very promising nutritional fortifiers (Liu et al., 2023). Compared to previous reviews on chitosan (Chen et al., 2023; Shahbaz, Basharat, Javed, Bibi, & Yu, 2022; Crivei et al., 2026), this review provides an integrated perspective on the tailored preparation, multifaceted bioactivities, and promising food-industry applications of chitosan and its derivatives, while critically assessing mechanistic gaps and outlining future strategies for precision applications.

2. Preparation of chitosan and its derivatives

The production of chitosan is fundamentally a process of chemical modification, which centers on the deacetylation of chitin via alkaline thermal treatment. In conventional production, the DD and MW of chitosan are precisely controlled by adjusting alkali concentration, temperature, and reaction time. However, this process causes severe pollution from corrosive wastewater and impairs product quality through chain degradation and property inconsistency (Gao et al., 2024). Chitin can also be converted into chitosan through biocatalysis using chitin deacetylase. This method offers mild reaction conditions, high specificity, and environmental friendliness. However, it is limited by high enzyme cost and slow reaction rates (Zhang et al., 2023). Recently, greener approaches have been evaluated for the production of chitin and chitosan from insect-derived materials such as exuviae and cocoons, including biological methods, green solvents, and advanced processing techniques (Mersmann, Souza, & Fernando, 2025). The preparation of COS from chitosan involves a degradation process to yield products with low DP and better water solubility (Fig. 1). In recent years, a growing number of studies have investigated the preparation methods of COS (Zhou et al., 2021). The most commonly employed methods for COS production include: (1) chemical degradation, (2) enzymatic degradation, and (3) physical degradation (Table 1).

Fig. 1.

Preparation strategies for chitosan and COS from chitin by chemical, enzymatic, and physical methods.

Table 1.

Characterization of chitosan and its oligosaccharides preparation.

Categorization	Reaction conditions	Reaction products	Advantages	Disadvantages	References
Chemical Degradation	0.05 M HCl, 0.2 M H2O2, and 65 °C	Chitosan with a low MW (< 50 kDa)	Low cost, simplicity and scalability	Poor control over DP	(de Farias et al., 2019)
	15% acetic acid, 5 M sodium nitrite, and 15 °C	Monomer of hexoses	Simple and easy to perform	The product is only monosaccharide	(de Souza et al., 2022)
	4% H2O2, 30 °C, for 4 h	COS with an MW of 4.2 kDa	Significant reduce in MW of chitosan	Low productivity	(Tanasale et al., 2019)
	2% H2O2 solution at ambient temperature	COS (MW of 2–6.6 kDa)	High concentration of chitosan (10%, w/v)	Products heterogeneity	(Nguyen, Le, Tran, Bui, & Nguyen, 2023)
Enzymatic Degradation	Cellobiohydrolases	COS with a DP of 3–6	Readily available glycosidases	Poor substrate specificity	(Tegl et al., 2016)
	Chitosanase enzyme (BpCSN)	COS with a DP of 2–4	Wide adaptability to temperature and high activity	High cost	(Wang et al., 2023)
	Chitosanase (Csn46)	COS with a DP of 2–7	High DP COS products	Low thermal stability	(Wu et al., 2023)
	Chitinase (MyChi54)	N-acetyl COS, paCOS, and COS	Diversified products	Difficulties in product separation	(Sun et al., 2025)
Physical Degradation	Ultrasonication and formic acid	Low MW chitosan (32.81 kDa)	Suitable for industry production	The MW of COS is relatively high	(Suryani et al., 2022)
	Microwave heating degradation	Low MW chitosan (30 kDa)	Environmentally friendly and low cost	The MW of COS is relatively high	(Wasikiewicz & Yeates, 2013)
	Microwave induced plasma desorption/ionization (MIPDI) technology	Low MW COS (≤ 10 kDa)	Fast and green processing method	Products heterogeneity	(Li et al., 2021)
	UV-light irradiation	Low average MW of chitosan	Convenient, easy to operate, and cost-effective	The rate of depolymerization is low	(Suhaimi et al., 2025)

2.1. Chemical degradation

Common chemical reagents used to depolymerize chitosan include hydrochloric acid, acetic acid, nitric acid, and hydrogen peroxide. Under acidic conditions, the oxygen atom in the glycosidic bond of chitosan undergoes protonation, resulting in the cleavage of the bond and random scission of the polymer chain. This process yields a mixture of COS with varying DP. de Souza et al. conducted chitosan depolymerization using nitrous acid. The highest degradation rate was achieved under conditions of 5 M sodium nitrite, 15% acetic acid, and 15 °C (de Souza et al., 2022). A series of COS with varying MW was obtained by treating chitosan in 5% acetic acid for different durations. The analysis demonstrated that extended heating time resulted in a reduction of the MW of chitosan. The concentration of acid, treatment time, and reaction temperature have a great influence on the physical properties of COS, such as DD and MW. Furthermore, chitosan was depolymerized by changing the concentration of H₂O₂. The degradation of chitosan using 4% H₂O₂ at 30 °C for 4 h resulted in a 97.57% yield rate of COS with an MW of 4200 Da (Tanasale, Bijang, & Rumpakwara, 2019). Recently, advanced oxidation processes (AOPs) have emerged as an eco-friendly and efficient approach, utilizing reactive oxygen species to destabilize glycosidic linkages and thereby facilitate the subsequent hydrolysis and scission of chitosan polymer chains (Suhaimi et al., 2025). de Farias et al. obtained low MW chitosan using the acid pathway and oxidative pathway. The acid-catalyzed depolymerization was performed by dissolving chitosan in hydrochloric acid solution with a final acid concentration of 5.15 M. The oxidative pathway first dissolved chitosan in 0.05 M HCl, then continuous stirring at 65 °C was applied with the addition of 0.2 M H₂O₂. Both methods could yield chitosan with a low average MW (< 50 kDa) (de Farias et al., 2019). Chemical degradation, particularly the acid-catalyzed reaction, is widely employed in industrial production due to its operational simplicity, controllable conditions, and low cost. However, it suffers from poor control over the DP, product heterogeneity, and the generation of hazardous acidic waste, raising environmental concerns. Oxidative degradation offers a cleaner alternative but shows limited productivity and difficulty in controlling molecular weight distribution. These factors undermine its scalability for high-purity food-grade applications.

2.2. Enzymatic degradation

Enzymatic preparation of COS is presently viewed as the most advanced and promising method. This process employs non-specific and specific enzymes to selectively and efficiently cleave the glycosidic bonds of chitosan, which makes it particularly suitable for the applications in the food industry. Lytic polysaccharide monooxygenases (LPMOs) have recently emerged as a powerful tool for the oxidative degradation of chitin, enabling efficient and environmentally friendly conversion of this biomass resource. Ma et al. characterized an auxiliary activity family 15 (AA15) LPMO from the termite Cryptotermes secundus. This enzyme was shown to effectively bind and oxidize crystalline chitin, with an optimal temperature of 40–50 °C under acidic conditions (Ma et al., 2026). Tao et al. investigated the chitosanolytic activity of pepsin and proved the viscosity of the chitosan solution declined in a negative exponential manner following the addition of pepsin (Tao, Wei, Mao, Zhang, & Xia, 2005). Tegl et al. utilized the readily available cellulase to degrade chitosan, which yielded COS with a DP of 3–6 and varying DD (Tegl et al., 2016). The low substrate specificity of non-specific enzymes restricts their application, thus identifying chitosanases with higher specificity remains an urgent goal. Wang et al. isolated a strain of Bacillus paramycoides BP-N07 from a marine mud sample, which produced a chitosanase capable of the efficient degradation of chitosan into chitobiose, chitotriose, and chitotetraose (Wang et al., 2023). Wu et al. employed a comprehensive computer-aided mutant design strategy to modify chitosanase for enhanced thermal stability, resulting in several thermostable mutants. The mutant Mut4 demonstrated potential for industrial-scale food production of COS with a desirable DP (Wu, Yu, Zheng, Chen, & Wu, 2023). Xu et al. cloned a novel glycoside hydrolase family 46 chitosanase (CscB) from Kitasatospora setae KM-6054 and achieved its heterologous expression in Escherichia coli. This enzyme was identified as a cold-adapted chitosanase, producing final degradation products primarily with a DP ranging from 2 to 4, which provided an efficient enzymatic tool for the clean production of COS (Xu, Wang, Zhu, Yao, & Jiang, 2023). In addition to the chitosanases mentioned above, it has also been demonstrated that chitin and chitosan can be converted to COS by chitinase (Hellmann, Marongiu, Gorzelanny, Moerschbacher, & Cord-Landwehr, 2025). A novel glycoside hydrolase family 18 chitinase (MyChi54) with potential for COS preparation was obtained and characterized. The enzyme exhibited maximal activity at pH 5.0 and 45 °C, generating the products of five types of COS (Sun et al., 2025). Enzymatic degradation using specific chitosanases or chitinases provides superior selectivity, enabling the production of COS with well-defined DP (2–8) and high purity, which are critical for functional food ingredients. Nonetheless, its industrial scalability is hampered by high enzyme production costs, limited operational stability, and slow reaction kinetics. To overcome these barriers, future efforts should prioritize protein engineering for enhanced specificity and stability, coupled with AI-guided design and process intensification, ultimately aiming at scalable and sustainable manufacture of structurally defined COS.

2.3. Physical degradation

Physical degradation primarily involves the application of ultrasonic and microwave energy to disrupt intermolecular interactions and cleave glycosidic bonds, thereby achieving depolymerization of chitosan. Feng et al. successfully depolymerized chitosan by ultrasonic degradation in acetic acid solution. After treatment with sodium carbonate solution and distilled water, the final COS product was obtained (Feng et al., 2021). Ultrasonication combined with formic acid was utilized to depolymerize chitosan at 20 °C for 30 min. The yield rate of COS was 89.40% with an average MW of 32.81 kDa and a DD of 98.08% (Suryani et al., 2022). Under microwave irradiation (9 MJ/kg) with minimized thermal effects, chitosan in an acetic acid solution was degraded to an MW of 30 kDa within 20 min (Wasikiewicz & Yeates, 2013). For the first time, microwave-induced plasma desorption/ionization (MIPDI) was employed to prepare low MW COS. This approach enabled the degradation of native chitosan (540 kDa) into a soluble form (≤ 10 kDa), achieving a yield rate of 61% within 60 min (Li et al., 2021). Dong et al. systematically compared the effects of low-frequency probe sonication (US-L), high-frequency ultrasound plate (US-H), and ultrasound-microwave combined reactor (US-MW) on chitin. US-H and US-MW outperformed US-L, achieving comparable deacetylation to that of the conventional method (15 min vs. 3 h). This work highlighted US-MW as a particularly promising, rapid, and scalable approach for sustainable chitosan manufacturing (Dong et al., 2026). Physical degradation methods offer rapid processing, solvent-free operation, and tunable molecular weight reduction, making them environmentally attractive. However, they suffer from high energy input and poor selectivity toward specific chain lengths. Physical approaches are effectively integrated with chemical or enzymatic methods, resulting in accelerated degradation rates, lower consumption of acids or enzymes, and shorter reaction times.

3. Biological activities of chitosan and its derivatives

The functional amino and hydroxyl groups in chitosan and its derivatives contribute to a diverse range of biological activities, including health-beneficial properties, antimicrobial activity, antioxidant capacity, immunoregulation, film-forming ability, and biocompatibility.

3.1. Promoting nutrient absorption and animal growth

Nutrients are essential substances that organisms convert into structural components and the necessary energy for sustaining life. Plasma metabolomic profiles reveal that COS (DP = 2–6, DD = 88%) exerted a regulatory effect on loperamide-induced constipation in mice by down-regulating the abnormal expression of aromatic-L-amino-acid decarboxylase, which catalyzes the decarboxylation of aromatic-L-amino-acids to generate bioactive amine derivatives (Zhang et al., 2022). The impact of late-gestation COS (DP = 2–7) supplementation on placental amino acid transport was investigated in sows. COS enhanced the expression of amino acid transporters by activating the mTOR signaling pathway in the placenta (Xie et al., 2016). Dietary COS (DP = 2–7) supplementation also increased the small intestinal mucosal contents of Cys, Asn, Orn, and Asp in weaned piglets (Yang, Xiong, Li, & Yin, 2016). Therefore, dietary COS supplementation enhanced animal growth by elevating the availability of amino acids for metabolic utilization. Additionally, COS (DP = 4–7) promoted glucose uptake in a dose-dependent manner via both insulin-dependent and insulin-independent signaling pathways in C₂C₁₂ myotubes, involving the activation of insulin receptor substrate 1 and protein kinase C in the former, and liver kinase B1, AMP-activated protein kinase, and mTOR in the latter (Ha, Park, & Shon, 2016). COS (MW < 1500 Da) markedly inhibited hepatic lipid accumulation and restored the elevated concentrations of blood glucose and fasting insulin to normal levels in mice. Gene-expression data revealed that COS improved functions associated with the intestinal barrier and glucose transport (Wang, Liu, Tang, Dong, & Feng, 2021). In a murine model of calcium deficiency, COS (MW = 5 kDa, DD ≥ 85%) was found to protect desalted duck egg white peptide‑calcium complexes from gastric degradation, thereby facilitating greater calcium delivery to the intestines and enhancing calcium absorption. Furthermore, COS promoted calcium uptake in intestinal enterocytes, which might contribute to a reduced risk of osteoporosis and improved gut health (Zhao et al., 2022). A healthy gastrointestinal tract promotes better nutrient assimilation and faster growth rates in animals. COS (MW ≤ 1000 Da, DD > 85%) supplementation significantly enhanced small intestinal villus height along with the activities of digestive enzymes (maltase, sucrase, and lactase) in weaned pigs. Moreover, dietary COS supplementation increased the mRNA levels of tight junction proteins (claudin-1, occludin) along with the Na⁺-glucose co-transporter 1 (SGLT1) in the jejunum (Wan et al., 2017). Similarly, the beneficial roles of COS (MW = 1000–2000 Da) on broiler growth performance were associated with improvement in intestinal morphology and barrier function. These improvements included increased duodenal villus height, a greater villus-height to crypt-depth ratio, and enhanced claudin mRNA expression in the jejunum and ileum (Li et al., 2019). Growth hormone (GH) and insulin-like growth factor (IGF) are critical polypeptide regulators that play a key role in promoting animal growth. Dietary COS supplementation increased serum IGF-I and GH levels and elevated muscle and hepatic IGF-I mRNA levels in early-weaned pigs (Tang et al., 2005). Dietary chitosan (DD = 80%) supplementation also upregulated the expression of the growth hormone gene in the brain and liver tissues of stellate sturgeon (Acipenser stellatus) juveniles (Zakeri, Pazooki, Mohseni, & Jamshidi, 2024). As shown in Fig. 2, the efficacy of chitosan and its derivatives in promoting nutrient absorption and animal growth operates through three key mechanisms: (1) enhanced absorption and utilization of key nutrients (e.g., amino acids, glucose, and Ca²⁺); (2) improved intestinal function via increasing villus height and tight junction proteins; and (3) upregulated growth-promoting hormones (GH and IGF), collectively accelerating animal growth.

Fig. 2.

Mechanisms for nutrient absorption and growth promotion. CS and COS activate amino acid transport, glucose uptake, and Ca²⁺ absorption. They improve the intestinal barrier and elevate GH/IGF-I, collectively driving anabolic growth.

3.2. Modulating microbiota

Chitosan and its derivatives are well-established antimicrobial agents, with demonstrated efficacy against both bacteria and fungi. Staphylococcus aureus and E. coli are common pathogenic bacteria. COS (MW = 1 kDa, DD = 98.69%, DP = 3–7) exerted antimicrobial effects by binding to the cell envelopes and perturbing the integrity and permeability of the bacterial cell membrane. This ultimately led to the inactivation of E. coli through a sublethal injury process. In contrast, for S. aureus, COS exposure induced a portion of cells into a viable but nonculturable (VBNC) state, resulting in incomplete inactivation (Meng, Ma, Liu, Mao, & Li, 2022). Pseudomonas aeruginosa, a Gram-negative bacterium commonly found in healthcare environments, is well known for its ability to form biofilms. Chitosan (DD = 93.98%) exhibited a marked synergistic antibacterial effect against P. aeruginosa, significantly attenuating the production of pyocyanin and rhamnolipids, as well as reducing swimming motility, protease activity, and biofilm formation capacity (Riahi, Mabudi, Tajbakhsh, Roomiani, & Momtaz, 2024). Salmonella infection typically presents with gastrointestinal symptoms, such as vomiting, diarrhea, and abdominal cramps. Chitosan inhibited the clinical signs of Salmonella infection and decreased viable bacterial colonization in the tissues and feces of broiler chickens (Park et al., 2023). Vibrio cholerae is the bacterium responsible for cholera, which can cause a severe and potentially fatal diarrheal disease. Administration of COS attenuated intestinal colonization and disease severity of V. cholerae in mice via blockade of the ChsR-mediated pathway (Liu, Miao, Liu and Jiang, 2024, Liu et al., 2024). Aeromonas hydrophila is a Gram-negative bacterium known to cause a range of illnesses, including food poisoning, waterborne diseases, and infectious diarrhea. Chitosan mitigated the adverse symptoms induced by A. hydrophila challenge and protected hybrid sturgeon from bacterial invasion (Xu et al., 2023). The antifungal effect of COS (DD = 95.6%, DP = 3–6) was evaluated against Aspergillus flavus and Aspergillus fumigatus via quantifying the inhibition of mycelial growth. COS induced significant morphological alterations in the mycelia, including obvious wrinkling, deformation, and a fragmented appearance (Ke et al., 2022). In addition, chitosan and its derivatives exhibited significant prebiotic properties and were effective in modulating and balancing the gut microbiota of animals (Chen et al., 2022). Recent studies have demonstrated that chitosan (DD = 91.2%, MW = 1231 Da) exhibits prebiotic-like properties and promotes the growth of key probiotics such as Lactobacillus and Bifidobacterium in hamsters. These microbes are crucial for intestinal health by converting prebiotics into major short-chain fatty acids (SCFAs), including butyrate, propionate, and acetate (Abdo et al., 2023). Chitosan (DD = 85%) supplementation reshaped the composition of gut microbiota in cats. This alteration was characterized by a marked increase in the beneficial bacterium Allobaculum, a significant rise in fecal acetate and butyrate, and a concurrent suppression of pathogenic bacteria (Mo et al., 2023). The gut-immune axis refers to a bidirectional communication network between the immune system and the gut microbiota. Chitosan improved a healthy balance of gut bacteria, thereby achieving optimal immune responses (Edo et al., 2025). Moreover, administration of chitosan increased the goblet cell numbers and tight junction protein expression in the colon, while elevating SCFA levels in cecal contents. This modulation of the gut-brain axis consequently alleviated neurological abnormalities in mice (Bazaz, Padhy, & Dandekar, 2025). As shown in Fig. 3, the efficacy of chitosan and its derivatives in modulating microbiota is exerted through three principal aspects: (1) acting as effective antimicrobial agents; (2) displaying significant prebiotic properties; and (3) regulating gut-brain axis.

Fig. 3.

Microbiota modulation: antimicrobial and prebiotic actions. CS and COS disrupt bacterial membranes and virulence factors. They also promote beneficial microbes that produce SCFAs, which inhibit pathogens and strengthen the gut barrier via the gut-brain axis.

3.3. Immunomodulatory activity

The immune system functions as a critical network that orchestrates immune responses through the coordinated interplay of immune organs, cells, and molecules. Recent studies have demonstrated that chitosan and its derivatives are capable of boosting immune function. Chitosan (DD > 75% and DD ≥ 90%) treatment downregulated the expression of CD80 and CD14, supporting its role in monocyte and macrophage differentiation. Furthermore, chitosan upregulated the inducible nitric oxide synthase (iNOS) expression, which is a marker associated with pro-inflammatory responses and M1 macrophage polarization (Valades-Aguilar et al., 2024). Treatment with individual COS (DP = 2–6) monomers enhanced both phagocytic and pinocytic activity of macrophage-like RAW264.7 cells toward E. coli and S. aureus. Chitobiose (DP = 2) and chitohexaose (DP = 6) exhibited the strongest activity in promoting cell proliferation and non-specific immunity (Chen et al., 2023). Furthermore, COS (DD = 95%, DP = 1–6) treatment induced dendritic-like differentiation in RAW264.7 cells, characterized by morphological transformation, upregulation of surface markers (B7.1, B7.2, and CD40), G₀/G₁ phase cell cycle arrest, and enhanced phagocytic activity. This differentiation pointed to a potential mechanism by which COS augmented cell-mediated immunity (Wu, Wu, & Tsai, 2015). The synergistic effect of COS (DD = 98.2%, MW = 1230 Da) with running exercise was demonstrated by enhanced organ development of spleen and lung in rats, coupled with a differential modulation of primary immune parameters. This combined regimen downregulated lactate dehydrogenase, serum interleukin 2 (IL-2), and splenic T-cell ratio, while concurrently upregulating total lymphocytes, blood T-cells, CD8⁺ T-cell ratio, and serum TNF-α (Xiong et al., 2020). Dietary supplementation of COS (DD ≥ 90%, DP = 2–8) in sows elevated the levels of immunoglobulin (Ig) M in both colostrum and umbilical cord blood. Moreover, it increased the serum concentrations of IgG, IL-10, complement 3, and lysozyme (LYZ) in their offspring (Duan et al., 2020). Dietary chitosan (DD > 95%, MW = 10 kDa) supplementation upregulated the expression of IL-1, IL-8, and lipopolysaccharide (LPS)-binding protein in the liver and intestine of Nile tilapia (Oreochromis niloticus), suggesting its potential as an effective immunostimulant in aquaculture (Linh et al., 2024). In a cyclophosphamide (CTX)-induced immunosuppressed mouse model, chitosan (DD = 85%, MW = 200 kDa) significantly elevated IFN-γ levels, a cytokine secreted by T helper cells, thereby facilitating cell-mediated immunity (Mudgal, Mudgal, Kinra, & Raval, 2019). Similarly, COS (DD ≥ 90%, DP = 2–8) preserved macrophages phagocytic function and maintained the structural integrity of the thymus and spleen in CTX-treated mice. This immunoprotective effect was associated with the modulation of primary immune factors, including a notable increase in IL-2 and TNF-α levels and a significant decrease in IL-4 (Li et al., 2023). Additionally, COS (DD = 95.3%, MW = 1000 Da, DP = 2–6) counteracted the immunosuppressive effects of CTX by restoring impaired lymphocyte proliferation, natural killer cell activity, TNF-α production, and the CD4⁺/CD8⁺ ratio. The increase in infiltrating macrophages and T cells accounted for the immunomodulatory effect of COS (Zhai et al., 2018). As shown in Fig. 4, the immunomodulatory effects of chitosan and its derivatives are mediated through both cellular and humoral immunity.

Fig. 4.

Immunomodulatory pathways. CS and COS activate cell-mediated immunity by driving M1 macrophage polarization, enhancing phagocytosis and NK activity, and restoring CD4⁺/CD8⁺ ratios. At the humoral level, they elevate immunoglobulins (Igs) and balance pro-inflammatory and anti-inflammatory cytokines.

3.4. Antioxidant activity

Oxidative stress, referring to an imbalance between oxidation and antioxidation, leads to elevated protease secretion and the generation of excessive oxidative intermediates. As a detrimental effect induced by free radicals in vivo, oxidative stress in food systems drives the deterioration of lipids, proteins, and pigments, leading to a loss of quality in flavor, color, and nutritional value. Chitosan, abundant in functional amino and hydroxyl groups, exhibits potent antioxidant capacity. Studies have demonstrated that both chitosan and its derivatives exert antioxidant function through scavenging free radicals and enhancing antioxidant enzyme activity (Mittal, Singh, Buatong, Saetang, & Benjakul, 2023). It is believed that the antioxidant effects of chitosan and its derivatives are closely associated with their degree of polymerization, degree of acetylation and sequence (Hao et al., 2021). In vitro, COS (MW < 32 kDa, DD > 95%) demonstrated stronger radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O₂⁻), and hydrogen peroxide (H₂O₂), as well as higher ferric reducing antioxidant power (FRAP) compared with butylated hydroxyanisole (Lan, Chang, An, & Zhao, 2019). In vivo, COS (MW < 32 kDa, DD > 95%) conferred protection against H₂O₂-induced oxidative damage, as demonstrated by elevating the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC), while decreasing the level of malondialdehyde (MDA) in serum, spleen, liver, and kidney (Lan et al., 2019). The impact of a COS-supplemented diet on the antioxidative capacity in growing beagles was investigated by Cheng et al. It was found that COS (MW < 1000 Da, DP = 2–7) supplementation significantly enhanced the activities of antioxidant enzymes, such as CAT, SOD, and GSH-Px (Cheng et al., 2023). The inclusion of chitosan (DD = 85.09%) in the diet significantly improved the antioxidant capacity in the serum, duodenum, and liver of laying hens. The observed increase in overall antioxidant capacity may be mediated through the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently enhanced the expression and activity of Nrf2-mediated phase II detoxification enzymes (Li et al., 2022). Similarly, COS provided significant cardiac protection by mitigating oxidative damage in doxorubicin-treated rats. This effect was attributed to the stabilization of MAPK-mediated Nrf2/ARE signaling, which enhanced the transcription of downstream cytoprotective genes and recovered cellular homeostasis (Zhang et al., 2019). Moreover, COS (MW < 3.9 kDa) inhibited pyroptosis-induced ROS and MDA release by upregulating Nrf2 expression and promoting its nuclear translocation, which subsequently elevated the levels of glutathione peroxidase 4 (GPX4) and SOD in mice (Lu et al., 2024). As shown in Fig. 5, the antioxidant efficacy of chitosan and its derivatives is attributed to the activation of the Nrf2/ARE signaling pathway, resulting in the upregulation of key antioxidant enzymes.

Fig. 5.

Antioxidant mechanisms. CS and COS activate the Nrf2/ARE antioxidant defense axis to upregulate SOD, CAT, and GPx, thereby reducing ROS and MDA levels.

3.5. Anti-inflammatory activity

An excessive or prolonged inflammatory response is a critical pathogenic driver of tissue damage and ultimately leads to organ failure, posing a significant threat to human health. Chitosan and its derivatives exert anti-inflammatory effects by mitigating inflammatory responses and related complications. This effect is mainly attributed to the inhibition of inflammatory mediator production and release (Zheng et al., 2023). Similarly, COS differentially regulated inflammatory mediators by increasing anti-inflammatory factors (IL-10 and TGF-β1) and decreasing pro-inflammatory factors (TNF-α and IL-6) (Xie et al., 2023). COS (MW = 1000 Da, DP = 3–7) protected bovine mammary epithelial cells (BMECs) from LPS-induced inflammation by inhibiting the excessive production of Toll-like receptor 4 (TLR4) and the inflammatory cytokines TNF-α, IL-1β, and IL-6, which demonstrated that COS has potential as a therapeutic agent for mastitis alleviation (Lin et al., 2025). In an experimental autoimmune uveoretinitis (EAU) mouse model, COS suppressed the expression of key EAU inflammatory mediators (IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17, TNF-α, and MCP-1), suggesting its potential in treating posterior uveitis (Hsu et al., 2020). In an interleukin 1β (IL-1β)-stimulated inflammatory model, COS (DP = 2–8) exerted obvious anti-inflammatory effects by inhibiting the expression of MMP13 and ADAMTS-5, while promoting the expression of COL2A and ACAN in chondrocytes, indicating its potential as a therapeutic agent for osteoarthritis (Cao et al., 2022). In a murine model of severe acute pancreatitis, COS (MW < 1 kDa) administration markedly reduced the levels of critical inflammatory cytokines (TNF-α, IL-1β, and MCP-1) in both pancreatic and ileal tissues. Furthermore, COS treatment reduced inflammatory infiltration in the pancreas, which was associated with the suppression of the TLR4/NF-κB and MAPK signaling pathways (Mei et al., 2021). COS (MW = 1500 Da, DD = 90%) alleviated dextran sodium sulfate (DSS)-induced chronic ulcerative colitis in mice by attenuating the inflammatory response, which was mechanistically linked to inhibition of the classic TLR4/STAT3/NF-κB signaling pathway (Guo, Liao, Zhu, Hu, & Wang, 2021). Furthermore, COS (DP = 2–6) attenuated NF-κB activation by inhibiting IKK phosphorylation and impairing the nuclear translocation of p65. COS inhibited JNK phosphorylation and promoted the degradation of the NLRP3 protein, which led to the subsequent blockade of caspase-1 activation and IL-1β maturation (Hu et al., 2021). The anti-inflammatory mechanisms of chitosan and its derivatives were mediated by restraining the MAPK and NF-κB signaling pathways, along with the inactivation of the NLRP3 inflammasome (Fig. 6).

Fig. 6.

Anti-inflammatory signaling networks. CS and COS block the TLR4/MAPK/NF-κB pathway to reduce TNF-α, IL-1β, and IL-6. Meanwhile, they inhibit the NLRP3/caspase-1 axis to delay IL-1β maturation.

3.6. Other biological activities

Beyond these well-documented biological activities, chitosan and its derivatives display a range of other properties, such as film-forming properties, gelling properties, adsorption and flocculation capacities, and potential health benefits. Its film-forming ability renders chitosan and its derivatives promising natural food preservatives and coating materials. Chitosan-based films exhibit excellent UV absorption, which helps protect food against lipid oxidation, thereby improving the shelf life and quality of a variety of foods (Edo, Yousif, & Al-Mashhadani, 2025). Chitosan-based materials serve as suitable inks for 3D/4D (bio)printing and hold potential for constructing advanced drug delivery platforms and tissue-engineered scaffolds (Edo, Yousif, & Al-Mashhadani, 2024). An eco-friendly composite adsorbent was synthesized by utilizing cellulose extracted from pomegranate peel waste and chemically cross-linked chitosan (MW = 190 kDa, DD = 75%), aimed at valorizing agricultural by-products for water remediation (Fadhil, Al-Mashhadani, Mortada, Alsayed, & Khalifa, 2026). COS increased calcium deposition, alkaline phosphatase activity, and osteoblast markers during mouse mesenchymal stem cell differentiation, indicating COS represents a promising candidate for the treatment of osteoporosis and related bone disorders (Vimalraj et al., 2024). In a murine model of alcohol-induced liver injury, COS (MW ≤ 3000 Da) administration mitigated hepatic steatosis and reduced inflammatory infiltration. This therapeutic effect was further demonstrated by the reduction of liver injury biomarkers, a concomitant increase in antioxidant enzyme activities, and a consequent significant improvement in overall liver function (Liu et al., 2025). In a hypercholesterolemic hamster model, COS (DD = 91.2%, MW = 1231 Da) intervention significantly reduced plasma total cholesterol (TC) and triacylglycerols (TG), along with favorable modulations in bile acid profiles and gut microflora related to cholesterol metabolism (Abdo et al., 2023). Rats were fed a high-fat diet to establish an obesity model and then administered COS (MW ≤ 1000 Da) for 8 weeks. The COS treatment effectively attenuated weight gain, suppressed adipose tissue hypertrophy and hyperplasia, and decreased the fat-to-weight ratio. Furthermore, COS alleviated liver lipid accumulation, demonstrating significant anti-obesity efficacy (Deng et al., 2020). Chitosan and its derivatives have become promising biomaterials for wound dressings due to their biocompatibility, oxygen permeability, hemostatic and antimicrobial properties. Recently, various chitosan-based self-healing hydrogel dressings have been developed to address increasingly complex wound conditions (Zhang, Liang, Huang, & Guo, 2024). As described above, the diverse biological activities of chitosan and its derivatives provide a solid foundation for their potential applications in the food industry.

4. Current applications of chitosan and its derivatives in food industry

Owing to their multifaceted bioactivities, chitosan and derivatives are widely used in food applications as nutritional ingredients, antioxidants, antibacterial agents, preservatives, nutrient carriers, and packaging materials. Mechanistically, immunomodulatory and prebiotic effects underpin gut-health ingredients, while antioxidant and antimicrobial properties enable natural preservation and active coatings, and enhanced absorption supports carrier systems. These functional roles are systematically discussed in Table 2.

Table 2.

Applications of chitosan and its derivatives in the food industry.

Application category	Model & Food matrix & Grafted compound	CS/COS form & Dosage	Core functional outcomes	Industrial merits & Limitations	References
Functional food ingredients	Adolescents with overweight (Oral chitosan powder)	CS: 3 g/d for 12 weeks	Improve obesity indicators, lipid markers, glycemic markers, and appetite-related hormones.	Safe, affordable, and marine-derived, but its effective dose is high.	(Fatahi et al., 2022)
	Ethanol-induced liver injury mouse model (Oral COS aqueous solution)	COS (MW ≤ 3000 Da, 1000 mg/kg)	Ameliorate steatosis and inflammatory damage in the liver, and attenuate alcohol-induced injury.	Show in vivo hepatoprotection, but with a high dose and a lack of clinical data.	(Liu et al., 2025)
	Acute gastric ulcer rat model (Oral aqueous solution)	CS (MW = 790 kDa, DD = 85.4%)	Reduce ulcer area and ulcer index, restore gastric pH, and enhance antioxidant enzymes.	Valorize crustacean shell waste into a high-purity, sustainable biomaterial, but with a complex extraction/purification process and a lack of degradation kinetics.	(Yang et al., 2025)
Antioxidants	Mango, grape, and apple slices	CS-based composite films (DD ≥ 95%)	Possess excellent antioxidant activity and prolong the shelf life of fruits.	Strong, antioxidant, and renewable, but with no in vivo data, color darkening, and scale-up uncertainty.	(Jia et al., 2025)
	Tuna oil-in-water multilayer emulsions	Chitosan (MW = 120 kDa, DD 75–85%)	MRPs enhance DPPH scavenging and antioxidant activity and form a cationic coating on lecithin-coated oil droplets.	One-step thermal process from food-grade, renewable biomaterials, but with complex reaction mechanisms and the potential formation of unidentified MRPs.	(Kaewtathip et al., 2022)
	2-chloromethyl-5-hydroxypyridone (HPO) and kojic acid	COS-HPO conjugates (MW = 1 kDa, DD = 94%)	Exhibit excellent free radical (DPPH•, ABTS+•, and •OH) scavenging activity and reducing power.	Improved thermal stability and non-cytotoxicity, but with multi-step synthesis and moderate yields.	(Zhang, Wu, et al., 2023)
Antibacterial agents	Chitosan powder, Schiff base (CHSB)	CS (DD = 75–85%, low MW)	Antibacterial activity against E. coli, S. typhimurium, S. aureus, and B. cereus.	Biocompatible, non-toxic, and biodegradable, but with multi-step synthesis and a lack of in vivo / real-food application data.	(Çelikçi et al., 2025)
	Geraniol (Ger) grafted to the C2 amino group of COS	COS (MW = 1.5 kDa, DD = 95%)	Enhanced antibacterial activity against both Gram-negative and Gram-positive bacteria.	Simple, green, and high-yield synthesis, but with poor solubility at pH > 7, and safety/toxicity in food matrices not yet evaluated.	(Bi et al., 2021)
	Terpenols grafted onto the O-hydroxyl groups of COS.	COS (MW = 1 kDa, DD = 90%)	Improved thermal stability and antibacterial activity, with more potency against Gram-positive S. aureus than Gram-negative E. coli.	Versatile route for grafting terpenols, retaining active amino groups of COS, but with multi-step synthesis and low overall yields.	(Yue et al., 2021)
Preservatives	Tilapia fillets; citric acid (CA) + choline chloride (ChCl)	CS film (DD ≥ 95%, viscosity 100–200 mPa·s)	A 5% coating maintains color, reduces moisture loss, preserves protein, lowers TVB-N, and extends shelf life at 4 °C.	Eco-friendly, biodegradable, and non-toxic components (CA, ChCl), but with further studies needed on migration, safety, and large-scale production.	(Shi et al., 2025)
	Cherry tomatoes; lignosulfonate (LS)	CS film (MW = 700–800 kDa, DD ≥ 90%)	The film maintains cherry tomato firmness, minimizes weight loss, reduces surface wrinkling, color change, and preserves TSS over 14 days.	Sustainable and eco-friendly, with improvement in mechanical strength and UV protection, but scale-up, cost-analysis, and end-of-life management are not yet evaluated.	(Zhu et al., 2024)
	Penaeus vannamei (shrimp); hydroxypyridinone (HPO)	COS conjugate (MW = 1 kDa, DD = 94%)	Shrimp preservation: Lowered pH rise, TVB-N, TBARS, and TBC; retarded color change; extended shelf life to 10 days.	Simple dipping application suitable for seafood processing, but long-term stability and regulatory approval are not addressed.	(Xu et al., 2025)
Transport carriers	Food processing enzyme	CS microspheres (Diameter < 1 mm)	Superior pH tolerance, thermal stability, and storage stability; it maintained ∼81% RNA hydrolysis conversion rate after 24 h.	It enables enzyme reuse (10 cycles) and is non-toxic, food-grade, and biocompatible as a carrier, but scalability and long-term industrial validation are still required.	(Yin et al., 2025)
	Retinol (vitamin A), l-ascorbic acid (vitamin C), α-tocopherol (vitamin E)	CS microspheres with a size range of 10–20 μm (DD = 85%)	The microspheres display 6 h sustained release without burst effect. Cumulative permeation of VA, VC and VE rise by 15–20%.	Natural, biodegradable, and biocompatible polymers with high loading efficiency and a sustained release profile, but some Schiff bases limit the usable dose, and scale-up and cost have not yet been evaluated.	(Lewicka et al., 2024)
	Oleanolic acid (OA) – natural pentacyclic triterpene from olives	COS micelles (MW ≤ 3 kDa, DD = 85%)	Slower release, protection from acidic degradation, and prolonged intestinal retention of oleanolic acid.	It has high drug loading and high encapsulation efficiency and enables oral delivery, but covalent synthesis (EDC/NHS) adds cost and complexity, and scale-up and regulatory path are not yet evaluated.	(Yuan et al., 2025)
Packaging materials	Aromatic aldehydes grafted onto chitosan via Schiff base reaction	Schiff bases derived from CS (MW = 50–100 kDa)	The material shows enhanced thermal stability, improved photostability, and potential for packaging/films requiring UV protection.	Simple, one-step modification and improved thermal and UV stability; but cytotoxicity or migration of Schiff base moieties has not been evaluated.	(Saleh et al., 2022)
	Blueberries; CS cross-linked with CCNF-PL via citric acid esterification	Composite aerogel of CS (DD = 90%)	These materials exhibit ultra-low density, high compressibility, and excellent shape recovery, showing significant potential for perishable fruit packaging applications.	The material is fully biobased, biodegradable, and non-toxic, but no evaluation of real-world humidity/temperature fluctuations or long-term storage has been performed.	(Liang et al., 2026)
	Grafted with Sauropus androgynus extract (SAE)	CS film (MW = 150 kDa, DD = 85%)	The film shows excellent inhibitory activity against foodborne microorganisms, indicating its potential as an effective food-packaging material.	Biodegradable, eco-friendly active packaging is a plastic alternative, but it has no in vivo food trial, and large-scale casting needs standardized upscaling.	(Wong et al., 2025)

4.1. Nutritional ingredients

Chitosan and its derivatives serve as valuable functional food ingredients due to their various biological activities (Gul, Khan, Latif, & Faqir, 2025). Chitosan (3 g/day, 12 weeks) binds negatively charged dietary fats, bile acids, and cholesterol into indigestible complexes that are ultimately excreted in feces. Consequently, it is widely utilized in dietary supplements and functional foods aimed at lowering blood lipids and maintaining healthy cholesterol levels (Fatahi et al., 2022). Chitosan and its derivatives selectively enhance the growth of beneficial gut bacteria such as Bifidobacterium and Lactobacillus, while inhibiting the proliferation of harmful bacteria (Edo et al., 2025). Furthermore, chitosan (MW = 790 kDa, DD = 85.4%) facilitates intestinal mucosal repair and enhances barrier function. Consequently, it is widely recognized as a prebiotic and is employed to modulate gut microbiota, alleviate diarrhea, and promote overall digestive health (Yang, Du, Chen, Li, & Zhang, 2025). Chitosan and its derivatives can activate immune cells such as macrophages and neutrophils, promote cytokine (e.g., interleukins) production, and regulate non-specific immune responses (Kou, Peters, & Mucalo, 2022). These effects support their application as functional ingredients to enhance immunity and provide adjunctive anti-infective benefits in health foods and beverages. Chitosan and its derivatives can chelate with minerals such as calcium, iron, and zinc to form soluble complexes in the intestinal tract, which enhances their bioavailability (Wei et al., 2021). This efficacy enables the application of chitosan and its derivatives as mineral absorption enhancers in functional foods (Yu et al., 2023). Furthermore, as bioactive substances, chitosan and its derivatives can be utilized in functional foods by stabilizing blood glucose (Liu, Miao, Liu, & Jiang, 2024), offering liver protection (Wang et al., 2023), and supporting cartilage health (Rawojć, Tadeusiewicz, & Zych-Stodolak, 2025).

4.2. Antioxidants

The antioxidant properties of chitosan and its derivatives stem from the active amino and hydroxyl groups in their chemical structures, which can directly scavenge free radicals and thus inhibit the chain reactions of lipid oxidation in food systems (Wang et al., 2024). Novel chitosan-based nanocomposite films (DD ≥ 95%, mean diameter 205.9 nm) extended the shelf life of milk at 25 °C by improving its antioxidant activity. This finding provides a potential approach for the high value-added commercial application of chitosan in food preservation (Mao, Zeng, Ren, Ye, & Tian, 2025). A composite film composed of chitosan (DD ≥ 95%), dialdehyde cellulose, and proanthocyanidin was fabricated. It demonstrated strong scavenging rates of 92.76% for DPPH radicals and 99.44% for ABTS radicals. The film-forming solution successfully prolonged the shelf life of mango, grape, and apple slices by nine days (Jia et al., 2025). A layer-by-layer hydroxypropyl methylcellulose/chitosan (MW = 310–375 kDa) coating obviously improved the quality of mandarin fruits by elevating antioxidant activities and organic acid levels. This edible coating method facilitates its straightforward application during the postharvest period (Jurić et al., 2023). The Maillard reaction products (MRPs) derived from chitosan (MW = 120 ± 98 kDa, DD = 75–85%) and corn syrup solids exhibited superior antioxidant activity compared to the native system. The developed MRPs with dual antioxidant and encapsulating functions can be employed to protect emulsified oil from oxidation (Kaewtathip, Wattana-Amorn, Boonsupthip, Lorjaroenphon, & Klinkesorn, 2022). Similarly, the complex of naringin and COS exhibited observably enhanced water solubility, reduced bitterness, and stronger antioxidant activity compared to pure naringin, making it ideal for broad application in food products (Cao, Li, Zhou, & Zhao, 2021). Two novel COS-HPO conjugates were obtained by reacting COS (MW = 1 kDa, DD = 94%) with 2-chloromethyl-5-hydroxypyridone (HPO), which exhibited excellent free radical (DPPH•, ABTS⁺•, and •OH) scavenging activity and reducing power, suggesting their potential applications in food preservation. Additionally, the conjugates were found to be non-toxic to RAW264.7 macrophages and MRC-5 human lung cells (Zhang, Wu, Wei, Xie, & Zhou, 2023). Modification with COS (0.15–0.60%, w/v) not only inhibited the oxidation of silver carp myofibrillar protein (MP) but also enhanced its solubility and foaming stability. This modification addressed the key challenge of fish protein denaturation during processing (Cong, Wu, Zhang, & Kan, 2023).

4.3. Antibacterial agents

Chitosan and its derivatives have demonstrated significant antibacterial efficacy against a variety of pathogens in the food industry. Chitosan (DD = 75–85%) and its Schiff base derivatives demonstrate antibacterial activity against both Gram-negative bacteria (E. coli and S. typhimurium) and Gram-positive bacteria (S. aureus and B. cereus). Their inhibitory effect is comparable to that of commercial drugs such as amikacin and gentamicin, suggesting their potential as viable alternatives or adjuncts for applications in the food industry (Çelikçi, Zıba, & Tümer, 2025). Chitosan nanoparticles (NPs) have attracted increasing attention as effective antibacterial agents. Their polymeric and bio-based property offers promising potential for applications in food preservation (Akdaşçi, Duman, Eker, Bechelany, & Karav, 2025). Grafting chitosan with phenolic acids improves its antibacterial activity. This enhanced efficacy of phenolic acid-grafted chitosan has been demonstrated across diverse food categories such as fruits, vegetables, and meat (Yang et al., 2023). The intrinsic antimicrobial properties of the COS/BSA coating collectively disrupt bacterial structural integrity. The BSA@COS coating readily adheres to the surface grooves of strawberries, extending their shelf life by nearly three times (Na et al., 2024). A novel COS (MW = 1.5 kDa, DD = 95%) derivative (COS-N-Ger), synthesized by grafting geraniol (Ger) onto the amino group of COS, exhibits significant antibacterial activity against E. coli and S. aureus. This COS derivative provides a reliable strategy for developing antibacterial agents in the food industry (Bi et al., 2021). Grafting cinnamyl alcohol (Cin) onto the hydroxyl groups of COS (MW = 1.5 kDa, DD = 82%) yields the derivative COS-O-Cin, which demonstrates superior thermal stability and enhanced antibacterial efficacy against E. coli and S. aureus compared with COS. These characteristics offer valuable support for the development of novel antibacterial agents in food preservation (Yue et al., 2020). A novel derivative of COS-O-terpenol (COS-O-Ter, MW = 1 kDa, DD = 90%) demonstrates excellent solubility and obvious in vitro antibacterial activity. This antibacterial effect is more significant against S. aureus than against E. coli, suggesting that COS-O-Ter holds promise as an effective antibacterial agent (Yue et al., 2021).

4.4. Preservatives

Chitosan and its derivatives are effective natural preservatives in the food industry. They maintain the quality and safety of perishable food by inhibiting microbial growth, enhancing antioxidant activity, suppressing enzymatic reactions, and providing barrier properties (Yu, Yu, Zhao, Regenstein, & Xia, 2022). A meta-analysis was performed to evaluate the effectiveness of chitosan in maintaining key quality parameters of seafood and meat. This research proved its significant potential as a natural alternative to synthetic preservatives for protein-rich perishables (Chen, Wu, Dong, & Yu, 2025). When used as a bioactive coating for tilapia fillets, chitosan (DD ≥ 95%, viscosity 100–200 mPa·s) films incorporated with citric acid-based deep eutectic agents significantly prevented water loss, maintained protein content, controlled total volatile basic nitrogen levels, and prolonged shelf life, demonstrating tangible preservation benefits (Shi et al., 2025). Chitosan/alginate composites have demonstrated significant potential in the postharvest preservation of fruits and vegetables due to their robust mechanical property, advantageous electrostatic interaction, and adaptable barrier functionality (Zheng et al., 2025). An edible coating formulated with grape juice and chitosan was developed to preserve the postharvest quality of Red Globe grapes. Application of the coating effectively prevented weight loss, minimized color changes, preserved soluble solids content, and inhibited microbial growth. This sustainable method obviously extended the storability of the grapes (López-Díaz et al., 2025). A flexible chitosan (MW = 700–800 kDa, DD ≥ 90%) film reinforced with lignosulfonate (LS) was shown to maintain the freshness and hardness of cherry tomatoes and inhibit weight loss. This investigation sheds new light on the preparation and application of CH/LS composite films in food preservation (Zhu et al., 2024). An appropriate concentration of COS (DD ≥ 90%) promoted the formation of a more continuous protein network structure, which maintained the internal integrity of cakes. This effect prolonged the shelf-life of the cakes by 3–6 days. These findings indicated that COS could improve the quality and storage stability of gluten-free food products (Zhu et al., 2025). A novel COS-hydroxypyridinone (COS-HPO) conjugate (MW = 1 kDa, DD = 94%) demonstrated potent antibacterial, antioxidant, and anti-tyrosinase activities. Treatment with COS-HPO extended the shelf life of shrimp to 10 days at 4 °C, indicating its potential for shrimp preservation (Xu, Wu, Xia, & Zhou, 2025).

4.5. Transport carriers

Chitosan nanoparticles, commonly prepared through ionic gelation, achieve high encapsulation efficiency for bioactive compounds such as essential oils. These nanoparticles have demonstrated considerable potential to control microbial growth and mitigate oxidative processes within food systems (Tuesta et al., 2025). Phlorotannins isolated from Sargassum ilicifolium were effectively encapsulated using a chitosan-tripolyphosphate carrier system. Analysis of the total phlorotannin content indicated that encapsulation might facilitate their targeted delivery to intestinal absorption sites (Kaushalya & Gunathilake, 2022). As an effective carrier, cross-linked chitosan microspheres (CSMs, diameter < 1 mm) were prepared with chitosan and glutaraldehyde (GA) for immobilizing nuclease P1 (NP1). The resulting NP1@CSMs-GA was applied to nucleotide production through RNA hydrolysis, exhibiting excellent reusability and stability in the food processing industry (Yin, Yang, & Yang, 2025). Ursodeoxycholic acid-modified COS (UCOS, MW ≤ 3 kDa, DD = 85%) was synthesized to encapsulate oleanolic acid (OA) into self-assembled nanomicelles (UCOS-OA). UCOS-OA demonstrated significant gastrointestinal stability and prolonged intestinal retention time compared with free OA. UCOS serves as a useful polymeric carrier for OA encapsulation, elevating its bioavailability and antidiabetic efficacy (Yuan et al., 2025). Bisdemethoxycurcumin (BDMC), a polyphenolic compound with nutritional benefits, was used with chitosan (MW = 310–375 kDa) to synthesize Ag nanoparticles, which were then functionalized to form BDMC-Ag-Ch hybrids with improved stability and porosity. This approach yielded crystalline structures favorable for nutritional delivery (Ahmad et al., 2024). Cyanidin-3-O-glucoside-loaded COS nanoparticles (encapsulation efficiency 53.88%, loading 5.11%, ζ = −19 mV) demonstrated high encapsulation efficiency and stability, indicating their suitability for use in nutraceutical and functional food applications (Sun et al., 2020). Chitosan (DD = 85%) and carrageenan were employed to develop microparticles with a size range of 10–20 μm for the controlled release of immobilized vitamins. The obtained microparticles exhibited a loading capacity of 70–97% and demonstrated sustained release over 6 h. Moreover, in vitro biological assays confirmed that the microparticles had no cytotoxic effects (Lewicka et al., 2024).

4.6. Packaging materials

Fossil-fuel-based materials pose risks to human health, animals, and ecosystems. In this context, chitosan and its derivatives, owing to their biocompatibility, biodegradability, modifiability, and renewability, represent a promising alternative to their petroleum-based counterparts for food-industry applications (Edo, Yousif, & Al-Mashhadani, 2026). Surface functionalization of chitosan with terephthalaldehyde, 2-aminopyridine, and metal oxide nanoparticles has been reported to improve photostability. The metal oxides enhance thermal stability and UV-blocking, which are critical for active food packaging to extend shelf life (Edo et al., 2026). Pullulan-carboxymethyl chitosan/PEO core-shell nanofibers showed improved thermal stability, enhanced mechanical strength, and notable antibacterial activity. In a preservation study on bass, these materials prolonged the shelf life from 9 to 15 days. This demonstrated their considerable potential as food-packaging materials, particularly for aquatic products (Duan et al., 2023). The modification of chitosan (MW = 50–100 kDa) with aromatic aldehydes not only acted as a photo-stabilizer but also improved the thermal stability of chitosan, making it more suitable for biodegradable films and packaging materials (Saleh, Al-Tikrity, Yousif, Al-Mashhadani, & Jawad, 2022). Chitosan/polyvinyl alcohol blended films demonstrated superior compatibility and satisfactory intermolecular interactions, positioning them as a sustainable alternative to traditional petroleum-based plastic packaging. These films exhibit significant potential for practical applications in food preservation (Zhang et al., 2024). A composite aerogel was fabricated by crosslinking chitosan (DD = 90%) with ε-polylysine-functionalized carboxylated cellulose nanofibers (CCNF-PL) via radial freeze-drying. The resulting radially structured CS/CCNF-PL aerogel exhibits ultra-low density, high compressibility, and excellent shape recovery, and thus shows significant potential for perishable fruit packaging applications (Liang et al., 2026). A chitosan (MW = 150 kDa, DD = 85%)-based film incorporating Sauropus androgynus extract (SAE) was obtained by solution casting (designated as SAE-SCF). The SAE-SCF showed excellent inhibitory activity against all tested foodborne microorganisms, indicating its potential as an effective food-packaging material (Wong et al., 2025). Nevertheless, certain concerns merit attention when applying chitosan and its derivatives (Zhong, Dong, Long, He, & Xiao, 2026). The cationic C₂-amino groups of CS/COS readily induce electrostatic coacervation with anionic food proteins, leading to film precipitation and compromised preservation. In industrial settings, acidic conditions protonate CS but hydrolyze its backbone, while neutral/alkaline environments cause coating cracking. High-temperature pasteurization cleaves grafted bioactive side chains, although Schiff-base modification can enhance thermal stability. These incompatibilities and processing sensitivities represent major industrial bottlenecks, which can be mitigated by tuning the DD, DP, and N/O hydrophobic grafting of chitosan.

4.7. Safety, regulatory status, and market trends of chitosan and its derivatives

Chitosan has received multiple Generally Recognized as Safe (GRAS) notifications from the U.S. Food and Drug Administration (FDA). The first GRAS affirmation for chitosan was issued in 2005 (GRN No. 000164), authorizing its use as an antimicrobial agent in meat and poultry products. In 2014, the National Health and Family Planning Commission (NHFPC) of China issued an official document (No. 6, 2014) approving chitosan oligosaccharides as a novel food ingredient, permitting its application in food production and processing. Chemically modified CS and COS derivatives constitute distinct chemical entities and therefore require independent safety evaluation. Their application in food systems hinges not only on improved functional properties but also on comprehensive toxicological assessment, migration testing, and regulatory approval. Future development of chitosan derivatives should prioritize low-toxicity natural grafting or cross-linking chemistry to reduce regulatory barriers and migration risks. Several chitosan- and COS-based commercial products are available on the market. Examples include Chimax-O (Amicogen), a chitosan oligosaccharide derived from Bacillus sp., produced as a freeze-dried powder for use in dietary supplements and food products in compliance with GMP; COS-YS, a chitosan oligosaccharide intended for incorporation into processed foods, including health foods, dietary supplements (capsules and tablets), and beverages; and ChitoClear® (Primex ehf), a shrimp-derived chitosan that has been the subject of FDA GRAS notifications.

5. Conclusion and prospect

Collectively, this review indicates a clear trend of increasing global demand for chitosan and its derivatives within the food industry. Chitosan and its derivatives possess a spectrum of beneficial properties and bioactivities, including the promotion of nutrient absorption and animal growth, regulation of gut microbiota, modulation of immune responses, reduction of oxidative stress, and alleviation of inflammation. This review summarizes the preparation methods and bioactivities of chitosan and its derivatives, with a focus on their applications and considerable potential within the food industry.

Despite exciting breakthroughs, three prominent bottlenecks severely restrict large-scale industrialization. First, most existing studies only validate phenotypic bioeffects, yet fail to decode precise structure-activity correlations between molecular weight, degree of deacetylation, substitution modification sites and targeted biological pathways, lacking in vivo tissue-level regulatory evidence. Second, unified industrial application specifications are absent. Optimal dosage, administration modes, and compatibility thresholds with other food matrices under different processing, storage and physiological conditions have not been quantified, which impedes standardized formula design for functional foods and edible coatings. Third, high-purity COS and site-specifically modified derivatives rely on expensive chitosanase biocatalysts or multi-step chemical separation, leading to unaffordable raw material costs for food manufacturers. Additional industrial transformation hurdles include poor water solubility of chitosan limiting its dispersion in aqueous food systems, and insufficient long-term safety toxicology data for modified derivatives to expand regulatory approval categories globally.

For future research and industrialization, interdisciplinary collaboration spanning materials chemistry, microbial enzymology, food nutrition and food engineering is urgently required to overcome current limitations. Academically, research should shift from phenomenological observation to deeper mechanistic exploration. High-throughput modification screening combined with omics technologies can elucidate structure-activity relationships, while engineering of efficient gene-edited chitosanases will reduce biocatalytic costs and enable homogeneous oligomer production. For industrial application, integrated green degradation technologies combining physical ultrasound or microwave pretreatment with mild enzymatic hydrolysis should be developed to simplify downstream purification and reduce energy and reagent consumption. Customized derivative products target segmented food demands. Long-term toxicological and dietary intervention clinical trials are necessary to provide safety data, accelerate novel food ingredient certification worldwide, and ultimately unlock the full industrial potential of sustainable, health-oriented chitosan biomaterials across the global food industry.

CRediT authorship contribution statement

Mingzhi Liu: Writing – original draft, Investigation, Conceptualization. Yujia Gao: Writing – original draft, Investigation, Conceptualization. Lihua Chen: Writing – review & editing, Supervision. Xinyue Yao: Writing – review & editing, Supervision. Zhuo Guo: Writing – review & editing, Supervision. Xiaokang Liu: Writing – review & editing, Supervision. Yuguang Du: Writing – review & editing, Project administration, Conceptualization. Qingsong Xu: Writing – review & editing, Project administration, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

Supplementary Fig. 1.

Structural relationship among chitin, chitosan, and COS. Chitin (GlcNAc) is deacetylated to chitosan (GlcN/GlcNAc), then hydrolyzed to COS (DP 2–20).

Data availability

Data will be made available on request.