The current study investigates the effects of polyphenolic extract from the leaf of Paullinia pinnata against CCl4 -induced oxidative stress and liver damage in female albino rats. Thirty albino rats were randomly distributed into six groups (A-F). Rats in group A were given 1 ml normal saline orally to serve as control. The rats in groups B, C, D, E, and F were respectively induced intraperitoneally with single administration of 1 ml/kg body weight (b. wt) CCl4 dissolved in liquid paraffin (1:1). Thirty minutes after induction, the rats in the respective groups were orally treated with normal saline, 50 mg/kg b. wt. Silymarin, 50, 100 and 200 mg/kg b. wt. polyphenolic extract from P. pinnata respectively, once daily for 7 days. Levels of liver function indices and the activities of antioxidant enzymes were determined. Administration of polyphenolic extract from P. pinnata significantly (p < 0.05) ameliorated CCl4-induced hepatotoxicity with respect to liver function indices, antioxidant and lipid peroxidation parameters. The biochemical changes observed were also consistent with histopathological observations on the rat liver, as architectural degeneration and severe cellular necrosis were restored after the administration of polyphenolic extract from P. pinnata in the treated groups. The study suggests that polyphenolic extract from P. pinnata is a potential hepatoprotective agent against CCl4-mediated hepatic injury through fortification of antioxidant defense mechanisms.