Abstract: Background　Cerium oxide nanozyme-based wound repair materials have been extensively investigated. Current strategies primarily enhance their bioactivity through exogenous modifications such as grafting and doping, which are often limited by complex synthesis and poor stability. Regulating defect states via grain boundary engineering represents a feasible approach to directly boost their catalytic performance; however, its efficacy in promoting wound repair has not been validated.Objective　To synthesize cerium oxide with nanoscale grain boundaries and fabricate a composite hydrogel, thereby exploring the potential of this strategy to enhance wound‑repair efficacy.Methods　Cerium oxide nanozymes with grain boundaries (CeO2‑GB) were synthesized via a solvothermal method, and their morphology and phase characteristics were examined by scanning transmission electron microscopy (STEM) and X‑ray diffraction (XRD). The morphology, mechanical properties, and in vitro degradation profile of the hydrogel were assessed using scanning electron microscopy (SEM), Fourier‑transform infrared spectroscopy (FTIR), mechanical testing, and inductively coupled plasma optical emission spectrometry (ICP-OES). Biosafety was evaluated by CCK-8 assay, live/ dead staining, and hemolysis test. The protective function against oxidative stress was demonstrated through reactive oxygen species (ROS) probing, F‑actin staining, Calcein‑AM staining, and scratch assay. In vivo wound‑healing efficacy was validated by wound closure rate, histological staining, immunofluorescence staining, and immunohistochemical staining in a rat dorsal wound model. Results　The CeO2‑GB nanozyme and its composite hydrogel were successfully prepared. The hydrogel exhibited enhanced protection against oxidative stress, effectively scavenging intracellular ROS, preserving cell morphology, and augmenting cell proliferation and migration (P＜0.05). In the rat dorsal wound model, the hydrogel promoted re‑epithelialization, collagen deposition, and ROS clearance, as well as regulated inflammatory cytokine expression and facilitated tissue cell proliferation (P＜0.05).Conclusion　By modulating the intrinsic structure of cerium oxide nanozymes, this study synthesized a CeO2 nanozyme with multiple grain boundaries and incorporated it into a hydrogel. In vitro and in vivo experiments confirmed its superior wound‑repair capacity, offering new insights and strategies for the development of novel wound‑repair materials.