To investigate the hepatoprotective activity of Asparagus racemosus against isoniazid-induced hepatotoxicity in male albino rats. Rats (n = 6 per group)were divided into four groups: saline-treated control, saline-treated control with A. racemosus extract (50 mg/kg), isoniazid treatment alone (100 mg/kg, intraperitoneal [i.p.]), and isoniazid-A. racemosus extract (50 mg/kg)administered orally as cotreatment. Animals were treated for 21 days and euthanized 1 h after the last drug administration. Evaluated body weight, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, g-glutamyl transferase, total protein, albumin, hepatic malondialdehyde content, superoxide dismutase, catalase, cytochrome P450 2E1 (CYP2E1)activity and glutathione (GSH). A. racemosus extract prevented isoniazid-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage, liver functional profile, significantly (p < 0.05)inhibited CYP2E1 activity, markedly attenuated oxidative stress by improved enzymatic, non-enzymatic antioxidants levels and mitigate malondialdehyde, lipid hydroperoxide significantly (p < 0.05). These results suggest that A. racemosus extract exerts its hepatoprotective activity by inhibiting the production of free radicals and acts as a scavenger, reducing the free radical generation via inhibition of hepatic CYP2E1 activity, increasing the removal of free radicals through the induction of antioxidant enzymes and improving non-enzymatic thiol antioxidant GSH.