Repair of infectious bone defects remains a serious problem in clinical practice owing to the high risk of infection and excessive reactive oxygen species (ROS) during the early stage, and the residual bacteria and delayed Osseo integrated interface in the later stage, which jointly creates a complex and dynamic microenvironment and leads to bone non-union. The melatonin carbon dots (MCDs) possess antibacterial and osteogenesis abilities, greatly simplifying the composition of a multifunctional material. Therefore, a multifunctional hydrogel containing MCDs (GH-MCD) is developed to meet the multi-stage and complex repair needs of infectious bone injury in this study. The GH-MCD can intelligently release MCDs responding to the acidic microenvironment to scavenge intracellular ROS and exhibit good antibacterial activity by inducing the production of ROS in bacteria and inhibiting the expression of secA2. Moreover, it has high osteogenesis and long-lasting antimicrobial activity during bone repair. RNA-seq results reveal that the hydrogels promote the repair of infected bone healing by enhancing cellular resistance to bacteria, balancing osteogenesis and osteoclastogenesis, and regulating the immune microenvironment. In conclusion, the GH-MCD can promote the repair of infectious bone defects through the programmed transformation of the microenvironment, providing a novel strategy for infectious bone defects.