Diabetes prevalence in Indonesia reached 19.465 million patients in 2021 and is predicted to increase to 40.7 million cases by 2045, with 15-25% of diabetic patients at risk of diabetic wounds and 15-30% threatened with amputation. This study aims to determine the optimal concentration of cerium oxide nanoparticles functionalized with glucose oxidase (CeO2@GOx) nanozymes for the treatment of diabetic wounds. CeO2@GOx was incorporated into chitosan/poly(vinyl alcohol) (CS/PVA) hydrogel composites via a freeze-thawing method and systematically evaluated through physicochemical characterization, enzymatic assays, in silico analysis, antibacterial in vitro and in vivo wound healing studies. Molecular dynamics simulations (200 ns) were employed to investigate the dynamic stability of the flavin adenine dinucleotide cofactor within the GOx active site (FAD@GOx), particularly its structural persistence in the presence of Ce atom, CS, and PVA. Complementary density functional theory (DFT) calculations were independently performed on Ce₄O₈ clusters, chitosan, and poly(vinyl alcohol) (PVA) to examine their electronic properties and noncovalent interaction characteristics. UV-Vis analysis revealed increased absorbance at 298 nm with increasing CeO2@GOx concentrations, while functional group analysis confirmed the presence of hydroxyl, amine, carbonyl, and cerium-related features. The hydrogel exhibited a uniform particle size distribution (PDI = 0.1703) and a degradation rate of 90.334%. Among the tested formulations, the CeO2@GOx 4:1 (w /w) hydrogel exhibited the highest TMB oxidation rate and catalase-like activity and demonstrated optimal diabetic wound-healing performance in vivo within 7 days. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See https://ivyspring.com/terms for full terms and conditions.