© 2022 Elsevier B.V.The current work is focused on the preparation of protein-mediated poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) copolymer as a self-template for in situ synthesis of hybrid gels. Gelatin, collagen, biotin, and L-arginine were used to create hybrid materials with adjustable swelling and elastic properties. Hybrid cryogels tended to swell more than hybrid hydrogels due to their porous nature. Collaged-doped cryogels had the highest swelling, whereas gelatin-doped hybrids showed enhanced elastic modulus. All hybrid gels exhibited pH-sensitive swelling to controlled release applications depending on the degree of protonation of –NH2 and –COOH groups in the side chains. At low pH conditions, hybrid cryogels exhibited a higher swelling tendency compared to hydrogels. Ion-stimulus-response of hybrid gels was studied to evaluate the effect of salt concentration and features of ambient ions on swelling. Depending on the polyelectrolytic or polyampholytic nature, the extent of swelling in NaCl and KCl solutions varied according to the charge distribution in the network chains. Hybrid gels showed excellent adsorption performance for methyl orange by the presence of epoxy, hydroxyl groups, amino and carboxyl groups providing sufficient active sites. Adsorption capacity of hybrid cryogels is higher than that of hydrogels. The removal rate 97/%, reached an equilibrium state in a short period, suggested that collagen-doped hybrid cryogels have a potential application to remove dyestuff from wastewater. In relation to the decrease of methyl orange concentration in solution, adsorption process followed pseudo-second-order kinetic model. Avrami model has provided a better experimental-calculated fit and adsorption thermodynamics analysis indicated that the adsorption was a spontaneous process with a negative standard free energy. The characteristic findings from this research will provide insights into the design and application of enoate-ester and protein-based combinations in the food, biomedical and cosmetic fields.