This work aimed to develop a novel chitosan based metal-organic polyhedrons (MOPs)/enzyme hybrid hydrogel with superior antimicrobial properties in wound healing treatment. Hybrid hydrogel was prepared by crosslinking glucose oxidase (GOx), vanadium metal-organic polyhedrons (VMOP-2) and chitosan using glutaraldehyde as crosslinker. The formed GVCS hydrogel was characterized by using various techniques, including FTIR, SEM, XPS, TGA and EDX. Data show that GVCS hydrogel was successfully obtained with uniform distribution of GOx and VMOP-2 in the hydrogel structure. Antibacterial tests show that GVCS hydrogel exhibits better bactericidal effect on both gram-negative bacteria (S. aureus) and gram-positive bacteria (E. coli) compared to other hydrogel samples because of its hydroxyl radicals generation capacity in the presence of glucose. MTT assay shows that the hydrogel presents good cell compatibility. In vivo experiments using an infected wound model indicate that GVCS hydrogel can effectively facilitate wound healing. Therefore, chitosan based MOPs/enzyme hybrid hydrogel could be most promising for antibacterial therapy in clinical applications. Display omitted