BACKGROUND/OBJECTIVES: This study aimed to evaluate the renal protective effects of black rice anthocyanins (BRAs) against renal injury in mice induced by D-galactose (D-gal). METHODS: The renal aging mouse model was established by thirteen consecutive weeks of subcutaneous injections of D-gal. The serum levels of urea nitrogen (BUN), creatinine (CRE), uric acid (UA), antioxidant enzymes (e.g., GSH-Px and SOD), and total antioxidant capacity (T-AOC), as well as the contents of inflammatory factors (IL-1β, IL-6, and TNF-α) in kidney tissues were evaluated. Additionally, the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins was examined. RESULTS: BRA treatment significantly reduced serum levels of BUN, and CRE increased the concentrations of antioxidant enzymes and total antioxidant capacity in renal tissues, and reduced the levels of inflammatory factors. Furthermore, BRAs restored the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins to normal levels and promoted the recovery of the renal tissue architecture. CONCLUSIONS: It was demonstrated that BRAs could potentially prevent and protect against kidney injury by modulating the Nrf2 and NF-κB signaling pathways, attenuating oxidative stress and inflammatory responses, and modulating the gut microflora. These findings provide a scientific basis for the application of BRAs as a natural bioactive substance in the field of nephroprotection, especially against the renal degeneration that accompanies the aging process.