This study investigates the development and application of a novel hydrogel, CeO2-Y@ZIF-8@Ge, to enhance diabetic wound healing. The hydrogel is designed to target the crosstalk between macrophage reprogramming and angiogenesis, thereby reducing inflammation and accelerating wound closure. The hydrogel is composed of zeolitic imidazolate framework-8 (ZIF-8) coated with cerium dioxide (CeO2) and encapsulated with Y-27632, a Rho-associated protein kinase inhibitor. CeO2 has superoxide dismutase and catalase activities, which help remove excess reactive oxygen species (ROS) and repair mitochondrial damage. Y-27632 inhibits mitochondrial damage and promotes endothelial cell proliferation. The hydrogel is encapsulated in a photocross-linkable hydrogel (GeEMA) with cationic quaternary ammonium salt groups to enhance antibacterial properties. In vitro and in vivo studies demonstrate that CeO2-Y@ZIF-8@Ge effectively reduces ROS, repairs mitochondrial damage, and modulates the NLRP3 and cGAS-STING pathways, leading to reduced inflammation and improved wound healing. The hydrogel shows promise as a versatile dressing for diabetic wounds, promoting angiogenesis and tissue regeneration.This study investigates the development and application of a novel hydrogel, CeO2-Y@ZIF-8@Ge, to enhance diabetic wound healing. The hydrogel is designed to target the crosstalk between macrophage reprogramming and angiogenesis, thereby reducing inflammation and accelerating wound closure. The hydrogel is composed of zeolitic imidazolate framework-8 (ZIF-8) coated with cerium dioxide (CeO2) and encapsulated with Y-27632, a Rho-associated protein kinase inhibitor. CeO2 has superoxide dismutase and catalase activities, which help remove excess reactive oxygen species (ROS) and repair mitochondrial damage. Y-27632 inhibits mitochondrial damage and promotes endothelial cell proliferation. The hydrogel is encapsulated in a photocross-linkable hydrogel (GeEMA) with cationic quaternary ammonium salt groups to enhance antibacterial properties. In vitro and in vivo studies demonstrate that CeO2-Y@ZIF-8@Ge effectively reduces ROS, repairs mitochondrial damage, and modulates the NLRP3 and cGAS-STING pathways, leading to reduced inflammation and improved wound healing. The hydrogel shows promise as a versatile dressing for diabetic wounds, promoting angiogenesis and tissue regeneration.