The proposed working hypothesis demonstrates the role of whole glucan particles (WGPs) in the enhancement of the tumoricidal activities of macrophages. While all activators, including the tumor microenvironment (using tumor supernatant for inducing tumor-associated macrophages; TAM), IL-4 (M2), and lipopolysaccharide (LPS) (M1), had an effect on upregulated Dectin-1 and increased glycolysis, LPS more prominently reduced mitochondrial activities when compared with tumor supernatant and IL-4. Then, Dectin-1 was further upregulated by WGP in non-LPS-activated macrophages (M2 and TAM) and further upregulated by WGP stimulation, leading to an elevation in glycolysis and mitochondrial activities partly through WGP-Dectin-1 activation. In parallel, the WGP-improved glycolysis was more prominent in M2 and TAM than in M1 (possibly due to the already high glycolysis present in M1) and is possibly correlated with enhanced tumoricidal activity in M2 and TAM, implying a glycolysis-dependent tumoricidal effect. The picture was created by BioRender.com and is available online: https://app.biorender.com/ (accessed on 7 August 2022).