Background Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes defined by progressive kidney damage and, ultimately, kidney failure. The growing prevalence of diabetes worldwide, coupled with lifestyle changes, has led to a rise in the incidence of DN, posing a significant public health and financial burden.Purpose This work aims to assess the therapeutic significance of yangonin on DN in an experimental rat model.Methods The experimental rats received 65 mg/kg of streptozotocin (STZ) to induce DN. The rats with DN were then treated with yangonin for 12 weeks. After the treatments had been completed, the body weight changes and blood glucose levels in the experimental rats were determined. The kidney dysfunction biomarkers, including creatinine, urea, uric acid, blood urea nitrogen (BUN), and marker enzymes, were assessed utilizing commercial assay kits. The concentrations of inflammatory cytokines and oxidative stress-related biomarkers were evaluated using assay kits. The renal tissues of experimental rats underwent histological study.Results The treatment of yangonin considerably elevated the body weight and subsequent reduction in glucose levels in the DN rats. Furthermore, the concentrations of renal dysfunction markers and marker enzymes were decreased by yangonin in the DN rats. The yangonin effectively reduced inflammatory response and oxidative stress by boosting the anti-oxidant levels in rats with DN. The histological analysis results further confirmed the therapeutic efficacy of yangonin against DN.Conclusion The current findings indicate that yangonin may effectively mitigate DN in rats, which highlights that yangonin possesses the potential to serve as an advantageous treatment option for DN.