The purpose of this study was to evaluate the hepatoprotective and antioxidant properties of piperine against D- galactosamine induced hepatotoxicity in mice. Hepatotoxicity was induced in mice by a single dose of galactosamine (700 mg/kg, i.p.) activities of serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate transferase (SGPT), alkaline phosphatase (ALP) and tumour necrosis factor-alpha (TNF-α) were estimated in serum while lipid peroxidation and antioxidant status were determined in liver homogenate of control and experimental mice. Galactosamine administration (700 mg/kg, i.p.) significantly (p<0.05) increased the levels of SGOT, SGPT, ALP, bilirubin, TNF-α and lipid peroxidation and caused depletion in antioxidant status. Piperine and silymarin treatment to D- galactosamine treated mice resulted in decreased SGOT, SGPT, ALP, bilirubin, TNF-α and lipid peroxidation levels alongwith an increase in antioxidant status. The study suggests that the hepatoprotective activity of piperine is significant at the dose of 25mg/kg as compared to the standard drug silymarin.