Protective effect of ethanol extract of Piper longum Linn. against monosodium glutamate (MSG) induced toxicity was studied. Rats, orally administered with MSG at a dose of 8 mg/g body weight for 20 consecutive days, showed an increase in liver weight and rate of lipid peroxidation. Glutathione (GSH) in serum, liver and kidney showed decreased concentration. Significant increase was noticed in activities of serum alanine amino transferase (ALT) and aspartate amino transferase (AST), levels of serum triacylglycerol, total cholesterol and urea. Histopathological examination of liver and kidney showed central venous congestion, diffuse degeneration and necrosis of hepatocytes in para cortical and midzonal areas of liver and diffuse cortical tubular degeneration of kidney. Oral administration of ethanol extract of P. longum fruits at 300 mg/kg body weight along with MSG significantly reduced the levels of lipid peroxides in serum, liver and kidney, serum AST activity, serum levels of triacylglycerol and total cholesterol. Though, there was an increase in the level of GSH in tissues it was not significant. However, the treatment failed to reduce the levels of ALT and urea. Examination of tissue sections also exhibited normal histological architecture of both the organs. The present study revealed that administration of P. longum provided significant protection to liver and kidney from the oxidative stress of MSG, though the dose rate was not sufficient to provide a complete protection.