Continuous oxidative stress and cellular dysfunction caused by hyperglycemia are distinguishing features of diabetic wounds. It has been a great challenge to develop a smart dressing that can accelerate diabetic wound healing through regulating abnormal microenvironments. In this study, a platelet rich plasma (PRP) loaded multifunctional hydrogel with reactive oxygen species (ROS) and glucose dual-responsive property is reported. It can be conveniently prepared with PRP, dopamine (DA) grafted alginate (Alg-DA), and 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol (ABO) conjugated hyaluronic acid (HA-ABO) through ionic crosslinks, hydrogen-bond interactions, and boronate ester bonds. The hydrogel possesses injectability, moldability, tissue adhesion, self-healing, low hemolysis, and hemostasis performances. Its excellent antioxidant property can create a low oxidative stress microenvironment for other biological events. Under an oxidative stress and/or hyperglycemia state, the hydrogel can degrade at an accelerated rate to release a variety of cytokines derived from activated blood platelets. The result is a series of positive changes that are favorable for diabetic wound healing, including fast anti-inflammation, activated macrophage polarization toward M2 phenotype, promoted migration and proliferation of fibroblasts, as well as expedited angiogenesis. This work provides an efficient strategy for chronic diabetic wound management and offers an alternative for developing a new-type PRP-based bioactive wound dressing.© 2023 Wiley-VCH GmbH.