This study assessed hepatoprotection by ethanolic extract of a wild edible mushroom (Macrocybe gigantea) towards carbon tetrachloride (CCl4) intoxicated hepatic damage in mice. The extract was orally administered to the animals with hepatotoxicity induced by CCl4 at a dose of 150 mg/kg once daily. Serum glutamate pyruvate tranaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and bilirubin content which was elevated due to CCl4 intoxication was significantly reduced by the extract. Standard drug Silymarin was used as reference. In CCl4 alone treated animals, lipid peroxidation was increased with decrease in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) levels which represents the hepatic antioxidant status. The hepatic antioxidant status was restored with the extract treatment. Administration of the extract of Macrocybe gigantea indicated significant suppression of CCl4 induced hepatotoxicity as confirmed by histopathological studies. Free radical scavenging and antioxidant activities may be the possible mechanism of hepatoprotection and may be conferred by the presence of high amount of phenolics compounds and flavonoids.