Due to their enhanced antibacterial activity and minimal cytotoxicity, nanocomposite hydrogels have been considered attractive materials for biomedical applications. Maleic acid was used as a crosslinker in the development of methylcellulose/PVP/ZnO nanocomposite hydrogels. FESEM, FTIR, EDX, hemolytic and antioxidant tests were carried out to evaluate the prepared nanocomposites. FESEM and EDX measurements confirmed the presence of ZnO nanoparticles in the polymer matrix. The DLS revealed testing that the particle's maximum diameter is 50.7 nm, confirming the particle size and stability of the biogenic ZnO NPs. ZnO NPs incorporated nanocomposites exhibited excellent biodegradability and enhanced antioxidant activity. MC/PVP/ZnO nanocomposites exhibited a significant zone of inhibition against E. coli and S. aureus bacteria. The results showed that the prepared nanocomposites have high porosity (>80%), swelling properties, and antioxidant activity (>35%). The hemolytic activity test demonstrates that the developed nanocomposites are nontoxic. These findings significantly support the use of these innovative MC/PVP/ZnO bio-nanocomposite dressings for wound healing applications.