Objectives: This study aimed to explore the secondary metabolites from the methanolic extract of Euphorbia retusa forssk, as it is known for its use in folk medicine and for being rich in bioactive molecules. Methods: The methanolic extractwas fractionated by different chromatographic techniques and the structures of the isolated compounds were elucidated by UV, ¹H and ¹³C NMR spectroscopy. Hepatoprotective activity of E. retusa extract was evaluated on CCl₄-induced liver damage in rats through biochemical assessment of serum ALT as well as MDA, GSH and NO. It was also evaluated through histopathological study of liver autopsy samples. Results: From the aqueous methanolic extract of Euphorbia retusa forssk. aerial parts seven known phenolic compounds; kamferol-3-O-β-D- glucopyranoside (1), quercetin -3-O-β-D- glucopyranoside (2), 3,3`dimethoxy ellagic acid (3), ellagic acid (4), gallic acid (5), kamferol (6) and quercetin (7) were isolated and identified by chromatographic and spectroscopic analysis. Administration of the extract (100 and 200 mg/kg body weight) significantly decreased the AST and ALT levels, inhibited the CCl₄ -induced elevated levels of NO and MDA and increased the level of hepatic GSH. A comparative histopathological study of liver exhibited almost nearly normal architecture as compared to toxicant group. Conclusion: Euphorbia retusaextract has shown to have hepatoprotective activityon CCl₄-induced liver damage in rats which might be attributed to its phenolic contents.