Objective: The present study evaluated the hepatoprotective activity of Methanolic Extract of Ipomoea reniformis (MEIR) in experimentally-induced hepatotoxic rats. Methods: Hepatoprotective activity of MEIR was studied against ethanol (4 g/kg p.o.)-induced hepatotoxicity rats. Silymarin (100 mg/kg p.o.) was used as a standard reference. The following parameters were evaluated; serum biomarkers such as Serum Glutamate Oxaloacetic Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), total and direct bilirubin, Total Protein (TP) and tissue antioxidant levels such as Glutathione (GSH) and Lipid Peroxidation (LPO). Results and conclusion: The control group did not exhibit increase in serum parameters, but ethanol toxicant group showed significant increase in serum parameters such as SGOT, SGPT, bilirubin (total and direct), and LPO, whereas GSH and TP levels were markedly reduced. Silymarin, MEIR low dose (200 mg/kg p.o.) and high dose (400 mg/kg p.o.) treated groups showed significant decrease in SGOT, SGPT, total and direct bilirubin, TB, LPO and increase in GSH and TP levels. Based on the study findings in serum marker enzyme levels and antioxidant parameters, it is concluded that MEIR possesses hepatoprotective activity.