This study was designed to evaluate the hepatoprotective and antioxidant effect of methanol extract of whole plant of Sesuvium portulacastrum on CCl4 induced hepatotoxicity in rats. Activities of liver marker enzymes, SGOT, SGPT and ALP, total protein, albumin, globulin, total, conjugated and unconjugated bilirubins at an oral dose of methanol extract of Sesuvium portulacastrum (150 and 300 mg/kg) showed a significant hepatoprotective effect. Regarding antioxidant activity, methanol extract of Sesuvium portulacastrum exhibited a significant effect showing increasing levels of SOD, CAT, GPx, GSH and GRD by reducing malondialdehyde (MDA) levels.