Biocompatible and degradable hydrogels have garnered interest in wound dressings due to their ability to absorb biological fluids with properties resembling natural tissues. In this study, polyvinyl alcohol (PVA)-chitosan (CS)cefazolin (Cef) hydrogels were prepared using the solution casting method. To optimize hydrogel properties (swelling and degradation), essential process parameters, including PVA concentration, CS concentration, blend ratio of PVA/CS, and glutaraldehyde (GA) percentage, were investigated using response surface methodology (RSM). Experiments were performed at different pH levels (7.4, 5.8, 9.2) related to skin pH in various healing phases. Drug release studies showed that Cefazolin release was highest at pH 9.2, making it highly beneficial for treating infections in high-pH wounds. At pH levels of 7.4 and 5.8, the release was moderate to low, indicating a controlled release profile. Cytotoxicity tests revealed higher cell viability in treated samples compared to controls over five days. Results indicated that CS and PVA concentrations had a significant impact on the response variables, with increased CS amounts leading to enhanced swelling and degradation. The optimized hydrogel is characterized by FTIR, XRD, TGA, FESEM, EDX, AFM, porosity, gel content, mechanical properties, and antibacterial activity. Morphological evaluation confirmed suitable surface roughness for cell growth and wound healing, highlighting its potential as a wound dressing. The apparent porosity and gel content of the hydrogel were 74.90 % and 95.74 f 0.6 %, respectively. Mechanical tests showed tensile strength, elastic modulus, and elongation at break at 8.75 MPa, 0.824 MPa, and 106.87 %, respectively. The antibacterial activity against Escherichia coli, Staphylococcus, and Salmonella was reported as 24.4 f 0.5 mm, 37 f 1 mm, and 32 f 1.5 mm, respectively. These results and optimized process parameters highlight its potential for industrial wound care applications.