Diabetic infected bone defect remains a great challenge in clinical practice, with delayed healing characterized by bacterial infection and cellular disfunction caused by oxidative stress. Hence, a novel self-healing multifunctional Ag@PEG-4OI/EXO hydrogel is introduced for improving healing of diabetic infected bone defect. 4-octyl itaconate, a derivative of the metabolite itaconate, has been proved that which performs antioxidant and mitochondria-protected properties. Simultaneously, the Ag