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According to International Diabetes Federation Diabetes Atlas statistics, diabetic retinopathy (DR) is the leading cause of vision loss in blinding diseases. The underlying cause of retinal vasculopathy progression in diabetic patients is hyperglycemia and hypoxia features in microvascular region. Hence, cyanobacteria are used as carriers to load both gold nanoparticles (Au NPs) with glucose oxidase‐like activity and iridium nanoparticles (Ir NPs) with catalase‐like activity, respectively (Cyano@Au@Ir). The Au NPs nanozyme first degrades glucose into hydrogen peroxide, which is further decomposed into H2O and O2 by the Ir NPs to complete the cascade hypoglycemic reaction. Based on the unique light transmittance of eyeball and the accumulation of light in the retinal area, the sustainable O2 production by Cyano greatly alleviates the hypoxia of microenvironment, leading to the decrease of angiogenic growth factor and hypoxia‐inducible factor expressions. Simultaneously, the highly expressed peroxide in the DR microenvironment can also be eliminated by Ir NPs for anti‐inflammatory property. Furthermore, it is demonstrated in DR animal model that Cyano@Au@Ir significantly reduces neovascular progression and vascular leakage. This novel treatment mode fundamentally degrades blood glucose, continuously supplies O2, and scavenges free radicals for comprehensive microenvironment regulation, providing inspirations for solving fundus complications of DR. [ABSTRACT FROM AUTHOR]