Amorphophallus commutatus var. wayanadensis is a red listed medicinal plant which has been used tradition-ally in Wayanad, India for various ailments like hemorrhoids and tumors. The hepatoprotective and antioxidant activity of aqueous extract of Amorphophallus commutatus var. wayanadensis (AEAC) was evaluated against carbon tetrachloride (CCl4) induced hepatotoxicity in swiss albino mice models. Hepatoprotective potential of AEAC was determined by estimating the levels of hepatic marker enzymes and histopathological studies. Antioxidant activity of the extract was estimated using antioxidant enzyme activities and lipid peroxidation in the liver samples. AEAC showed significant reduction in the hepatic marker enzymes in the serum samples and increased the antioxidant enzyme activities compared to the CCl4 group. Histopathological analysis also confirmed the hepatoprotective activity of the extract. Qualitative phytochemical screening revealed the presence of saponins as major phytoconstituent, which might be responsible for the hepatoprotective and antioxidant activity of the extract. © 2015 Scientific Publishers. All Rights Reserved.