Critical-sized bone defects are usually accompanied by bacterial infection leading to inflammation and bone nonunion. However, existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, a degradable material with continuous ROS modulation is proposed, defined as a sonozyme due to its functions as a sonosensitizer and a nanoenzyme. Before degradation, the sonozyme can exert an effective sonodynamic antimicrobial effect through the dual active sites of MnN4 and Cu2O8. Furthermore, it can promote anti-inflammation by superoxide dismutase- and catalase-like activities. Following degradation, quercetin-metal chelation exhibits a sustaining antioxidant effect through ligand-metal charge transfer, while the released ions and quercetin also have great self-antimicrobial, osteogenic, and angiogenic effects. A rat model of infected cranial defects demonstrates the sonozyme can rapidly eliminate bacteria and promote bone regeneration. This work presents a promising approach to engineer biodegradable materials with long-time effects for infectious bone defects. Existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, the authors develop a degradable material with continuous ROS modulation, which rapidly eliminates bacteria and promotes bone regeneration in infected cranial defects.