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Background and Aim: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver. Materials and Methods: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1β (IL-1β) were evaluated. Results: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1β in extract-treated groups was observed. Conclusion: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property.