Objective: The present study was undertaken to evaluate the hepatoprotective activity of 4-hydroxyisoleucine enriched extract of Trigonella foenum-graecum and silymarin in the presence of piperine, against experimentally induced liver injury. Methods: Wistar albino rats (150-180g) of either sex (n=6) were employed in present study. Experimental hepatotoxicity was induced by the administration of paracetamol (3 g/kg, p. o. ). All the test drugs were administered orally in the form of suspension to the animals. The combination of silymarin and piperine, 4-hydroxyisoleucine (28%) enriched T. foenum graecum extract and piperine were given to animals to compare with individual group as well as with toxicant. Results: Administration of paracetamol caused significant increase in of SGOT, AST, ALP, bilirubin and total proteins characterizing experimental hepatotoxicity. 4-Hydroxyisoleucine enriched extract of T. foenum-graecum and silymarin in the presence of piperine, significantly attenuated the toxic effects of hepatotoxicants in liver. Histological study of liver was also carried out to estimate the extent of tissue injury. Conclusion: The combination of piperine and silymarin has shown significant hepatoprotective activity against the injury induced by paracetamol. This was evident from significant reduction in serum enzyme AST, ALT, ALP and total bilirubin. These biochemical observations were also supplemented by histopathological studies of the liver.