Bacterial infection is one of the most significant impediments to wound healing. To treat wounds, non-biological and non-pharmacological interventions have gained increasing importance as they are easily translatable into clinical products. In this study, we developed a niacin metal-organic frameworks (NOFs)-laden hybrid hydrogel with self-healing ability for better wound healing. The copper based-NOFs (Cu-NOFs) and zinc based-NOFs (Zn-NOFs) were constructed and encapsulated into the self-healing hydrogels, which could prevent NOFs from directly interacting with protein-containing solutions (e. g., tissue fluid). The hydrogel was prepared by using four-armed benzaldehyde-terminated polyethylene glycol (BAPEG) and carboxymethyl chitosan (CMC). Our results showed that the hydrogel gained self-healing ability through reversible Schiff base reaction. In addition, after loading NOFs, the hybrid hydrogel exerted significant effects on antibacterial and antioxidant activities. The in vivo studies demonstrated that the hybrid hydrogel could alleviate inflammation and enhance the formation of granulation tissue, collagen and vascular tissue, thereby promoting wound closure in rats with E. coli -infected wounds. Overall, this study highlights the tremendous potential for the clinical implementation of NOFs-laden hydrogel with good self-healing, antibacterial and antioxidant properties in wound healing.