Wound infection causes irregular tissue closure, often with prolonged healing. Traditional therapies based on antibiotic delivery have resulted in reduced therapeutic efficiency and drug resistance. Such features make it highly desirable to develop an antibiotic-free material for wound infection in clinical applications. Herein, a self-healing antibacterial hydrogel was designed to realize the treatment of S. aureus-infected wounds. The design of the dynamic imine bond endows hydrogels with self-healing and adaptive properties, which could cover the irregular wound and improve the safety of administration. In addition, benefiting from quaternized chitosan, the designed hydrogels also present fascinating antimicrobial properties and favorable biocompatibility. The evaluation in a rat skin wound infection model indicates that the fascinating antimicrobial effect accelerates wound healing by the designed hydrogels. This facile design of an antibiotic-free material allows effective wound infection management, which may be promising in coping with other complex wound healings.