Background:Nutmeg a well-known spice used as a folk medicine in India to treat stomach ailments. Worldwide it is commonly used for food preservation and fragrance. Abundant references were given for nutmeg in ayurveda, unani, and siddha as a single drug or as an important constituent in formulations.Objective:In the present study, nutmeg aqueous extract (NMAET) was evaluated against isoproterenol (ISO)-induced hepatotoxicity and oxidative stress.Materials and Methods:Antioxidant enzymes, liver functions tests, and lipid profile tests were performed using standard procedures. Histological examination of liver was done by fixing in formaldehyde solution and hematoxylin staining.Results:Oral administration of NMAET effectively inhibited the ISO-induced changes in the activities of hepatic marker and antioxidant enzymes in plasma and heart tissue along with lipid peroxidation levels. The liver sections of ISO administered rats showed massive fatty changes, necrosis, ballooning degeneration, and broad infiltration of the lymphocytes and the loss of cellular boundaries; these changes were completely absent in groups treated with extract. Analysis of variance and Duncan's Multiple Range tests were used to perform statistical analysis.Conclusion:Results suggest that the NMAET possess significant potential as hepatoprotective and antioxidative agent against ISO-induced damage in rats.