Alcohol consumption is a major culprit in the production of reactive oxygen species that enhances lipid peroxidation in the liver. In the present study, we evaluated the effect of daily oral administration of methanol stem bark extract of Piptadenia africana in ethanol induced hepatotoxicity. Thirty six male rats were randomly assigned into six groups. Ethanol toxicity was induced by exposing the rats to 45% ethanol (4.8 g/kg bw) administered by oral gavage. After treatment for 8 weeks, the animals were sacrificed and biochemical parameters like lipid profile, enzymatic and non-enzymatic antioxidants, indices of liver toxicity such as aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP), extent of lipid peroxidation as well as histopathological examination of the liver sections were evaluated. Chronic alcohol administration caused marked injury to liver cells as seen on the liver sections as well as elevated serum levels of AST, ALT and ALP with concomitant increase in triglycerides, total cholesterol, low-density-lipoprotein cholesterol (LDL-c) and malonydialdehde (MDA). Decrease in antioxidant activities as well as high-density-lipoprotein cholesterol (HDL-c) was also noticed. Rats pretreated with plant extract prior to ethanol exposure had decreased levels of AST, ALT, ALP, triglyceride, total cholesterol, LDLc, MDA and enhanced levels of enzymatic and non-enzymatic antioxidants as well as HDL-c. Intake of P. africana at the dosage of 100 or 200 mg/kg bw in this study was able to ameliorate the toxic response to chronic ethanol consumption in rats and this could be attributed to its bioactive constituents.