The present study was undertaken to evaluate the role of Cressa cretica aerial part's extract on tissue-lipid peroxidation, antioxidant status and serum markers in experimental rat liver damage. The liver was damaged in experimental rats with the administration of 1:1 (v/v) mixture of CCl4 (carbon tetrachloride) in olive oil at the dose level of 1 ml/kg body weight on once a week, intra-peritoneally (ip). The methanol extract of Cressa cretica (50mg/kg and 100mg/kg) and standard drug- silymarin (25mg/kg) were given orally to rats from day 1 to 21. The extract of C. cretica produced significant (P<0.001) dose-dependent protective role on the altered hepatic- SOD (superoxide dismutase), CAT (catalase), GSH (glutathione reduced), GPx (glutathione peroxidase), LPO (lipid peroxidation) and cytochrome P-450 enzyme when compared with the toxic controls. Serum was also analyzed for AST, ALT (transaminases), ALP (alkaline phosphatase), γ-GTP (γ-glutamyl transpeptidase), LDHD (lactate dehydrogenase), total bilirubin and total protein levels. Cressa cretica extract also play a protective role by decreasing the activity of serum marker enzymes, total bilirubin and by increasing the total protein levels. The results were comparable with the standard drug- silymarin. From the above results, it can be concluded that the observed hepatoprotective role of Cressa cretica extract might be explained by its strong antioxidant capacity and ability of oxidative stress reduction due to the presence of triterpenoid saponins, alkaloids, total phenolics and flavonoids in the extract and/or its isolated purified compounds– n-octacosanol-1, β-sitosterol, 6-hydroxy-3,4-dimethyl coumarin, 6-methoxy-7,8-methylene dioxy coumarin, β-sitosterol-glucoside, quercetin, kaempferol and rutin.