Table 1.

Advantages and disadvantages of peptidomimetics and small molecules in drug discovery.

Peptidomimetics	Small Molecules
Advantages
Mimic the complex interactions of natural peptides with their receptors or other targets.	Can interact with a wide range of biological targets. Versatile tools in drug discovery
Like natural peptides, showed high specificity and selectivity for targets, fewer off-target effects, and reduced toxicity.	Better membrane permeability, easily cross the cell membranes, reaching intracellular targets.
Improved metabolic stability compared to natural peptides	Good oral bioavailability, more convenient for patients.
Disadvantages
Many peptidomimetics still suffer from poor oral bioavailability and may require parenteral administration.	Small molecules can be rapidly metabolized and excreted, sometimes requiring frequent dosing or leading to short half-lives.
Compared to small molecules, inadequate membrane permeability	High potential for off-target effects and toxicity.
Complex and expensive synthetic processes are barriers to large-scale production.	Limited capability to mimic complex and specific interactions of larger biomolecules like peptides.
They can sometimes elicit immune responses.	More prone to the development of drug resistance.