<p>The potential protective effects of Curcuma Radix on diabetic retinopathy were investigated through network pharmacology, molecular docking, and cellular experiments. Network pharmacology results identified four primary active ingredients and twenty key target molecules; Protein-protein interaction network analysis revealed that the core targets regulated by Curcuma Radix in DR include AKT2, RAF1, IL6, IRS1 and IGF1R. KEGG enrichment analysis indicated that Curcuma Radix may improve DR through the HIF-1 signaling pathway, FOXO signaling pathway, and VEGF signaling pathway. Molecular docking results indicated that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and naringenin exhibited favorable docking activities with the core targets AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R.The ARPE-19 cell experiment results indicated that the four active ingredients could enhance cell viability and mitigate oxidative damage. They exhibited significant gene expression regulation effects on AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R, which were consistent with the molecular docking outcomes.Through the HUVEC endothelial cell model, the protective effects of the two compounds on the cellular barrier were validated. Demethoxycurcumin and bisdemethoxycurcumin demonstrated protective effects on endothelial cells by modulating ICAM-1 and VCAM-1 to improve barrier damage.This study preliminarily revealed, through network pharmacology and experimental validation that four active components in Curcuma Radix modulated high-glucose-induced ARPE-19 cell models by regulating the gene expression of AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R. Two of these components also mitigated thrombin-induced endothelial cell barrier damage in the HUVEC cell model by regulating VCAM-1 and ICAM-1 expression, thereby providing protection against DR. This study provides a theoretical foundation for investigating the pharmacological basis and mechanisms underlying these effects.</p>