ObjectiveDiabetic nephropathy (DN) is a foremost complications among diabetic patients worldwide with growing prevalence and mortality rates annually. Nearly, 25–40% of diabetic patients suffer from DN. ObjectiveThe current research work was done to ascertain the therapeutic properties of ononin against the streptozotocin (STZ)-challenged DN in rats via alleviating oxidative stress and inflammatory responses. MethodologyThe DN was initiated to experimental rats via intraperitoneal injection of 60 mg/kg of STZ. Then DN animals were supplemented orally with three various doses of ononin at 10, 25, and 50 mg/kg once a day for 60 days. After the completion, the glucose level and bodyweight of the animals were recorded. The renal function markers like creatinine, BUN, uric acid, and microalbumin (U-mAlb) was assessed using hematological analyzer. The contents of IL-6, IL-1β, TNF-α, TGF-β1, and fibronectin was assessed using assay kits. The levels of ROS and antioxidant biomarkers were assessed using standard techniques and renal tissues were examined histologically. ResultsThe ononin treatment substantially improved the bodyweight and depleted the FBG level, BUN, creatinine, uric acid, and U-mAlb levels in the STZ-challenged DN animals. The levels of inflammatory and fibrosis factors i.e. IL-6, IL-1β, TNF-α, TGF-β1, and fibronectin was remarkably depleted by the ononin treatment. The ononin also decreased the ROS level and improved the GSH content, SOD and GPx activities in the STZ-challenged DN animals. The findings of histological study also confirmed the therapeutic roles of ononin against STZ-induced changes in renal tissues. ConclusionAltogether, our results from this study evidences the beneficial roles of ononin treatment against the STZ-initiated DN in animals via its antioxidant and anti-inflammatory properties. Hence, it could be the potential candidate in the future for the management of DN.