Objectives: Several heavy metals like lead acetate can accumulate in the body due to exposure to the metal for a prolonged period. One of the possible mechanisms involved with lead toxicity is oxidative stress is for which liver is the target organ. The primary aim of this study was to examine the hepatoprotective role of methanolic stem extract from the herb Cissus quadrangularis on induced lead acetate liver injury in female Wistar rats.Methods: The course of the study was for 14 days. The animals were separated into 5 groups: two being control and negative and the other 3 groups based on the dosage of the methanolic extract of the plant was given. The dosage of the plant extract given was once daily for all days of course study. During the last 7 days, lead acetate was injected in the animals (25 mg/kg of body weight). The sacrifice was done 14 days later and the blood and liver samples were taken, which is then used for different antioxidant enzymatic assays.Results: Significant reduced (p < 0.05) antioxidant levels and increased lipid peroxidation levels were observed in lead acetate treated group which was ameliorated by the action of extract from Cissus quadrangularis fusiformis. Histopathological study also supported the finding.Conclusion: The results of the different antioxidant enzymatic assays supported the hepatoprotective role of methanolic stem extract of the plant Cissus quadrangularis over induced lead acetate injury in wistar female rats.