Diabetic retinopathy is a severe diabetes complication leading to vision impairment and blindness primarily due to the disruption of insulin signaling in the retina. This study investigated the protective effects of blueberry anthocyanin extracts (BAEs) and its main component, anthocyanin-3-glucoside (C3G), in the retinas of diabetic mice and ARPE-19 cells under high-glucose (HG) conditions. The results showed that diabetic mice suffered significant weight loss, elevated glycemic levels, and increased retinal cell apoptosis after 10 weeks. Treatment with various doses of BAEs resulted in a significant reduction in glycemic levels, weight stabilization, decreased levels of inflammatory cytokines, and inhibition of retinal cell apoptosis. These findings suggested that BAEs possess hypoglycemic properties, potentially mitigating diabetes-induced retinal damage by modulating associated signaling pathways. Immunoblotting analysis revealed that persistent hyperglycemia impaired the Akt/GSK3β signaling pathway in diabetic mice, while high doses of BAEs significantly restored the function of these pathways and promoted GLP-1 release, enhancing GLP-1R expression in the retina and potentially mitigating retinal injury. Finally, studies on the effects of C3G on ARPE-19 cell models deficient in REDD1 under HG conditions showed that C3G protected cells from HG damage through the GLP-1R/Akt signaling pathway. In conclusion, this research provides valuable insights into the therapeutic potential of BAEs and C3G for managing diabetes-related ocular complications.