For the development of renal diseases, oxidative stress (OS) is reasoned to be one of the risk factors. For the treatment or prevention of the renal disease, the use of antioxidants could be a hopeful therapeutic mediation as they retard or block the oxidative reaction along with the inflammatory process. Luteolin (Lut) is a plant flavonoid, a pharmacologically active component normally found in glycosylated forms in basic perilla leaf, green pepper, celery, seed, honeysuckle bloom, and chamomile blossom; it exhibits antioxidant activity. In this investigation, we explored the nephroprotective activity of Lut on bisphenol A (BPA)-induced nephron toxicity in rats. Orally administering Lut (100 and 200 mg/kg) diminished BPA-induced anomalies in the kidney, blood urea nitrogen, creatinine, and serum uric acid levels. Lut therapy reduced the BPA-influenced generation of inflammatory mediators, inclusive of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. This was coupled with significant improvement in kidney histopathologic features. Lut enhanced the nuclear factor-like 2 (Nrf2) and heme oxygenase 1 (HO-1) expression, which showed protection against OS induced by BPA. The current outcomes of the study showed that Lut has a strong reactive oxygen species scavenging property and potentially decreases the lipid peroxidation as well as inhibits DNA damage in renal toxicity induced by BPA. In conclusion, the potential antioxidant effect of Lut may be because of its modulatory effect on the Nrf2/antioxidant response element (ARE)/HO-1 pathway, which means it protects the kidney from BPA-induced oxidative injury. © 2019 IUBMB Life, 2019.