Objective: A number of therapeutic agents possessing potent in vitro action against trophozoites of E. histolytica have been used to combat this disease but so far, these have been found to be too toxic or providing only symptomatic relief. Therefore it was planned to search the molecules from natural sources. Material andmethods: Fruits of the Xylocarpus granatummangrove were selected for the study and were collected from South Andaman Coast. Ethanol extract as well as four fractions (hexane, chloroform, n-butanol soluble and n-butanol insoluble fractions) were prepared and active principle gedunin was isolated from the active fraction. Results and discussion: The ethanol extract showed MIC 125 ìg /ml in our in-vitro studies, and in vivo showed 80% inhibition of trophozoites at the dose of 900 mg/kg body weight against Entamoeba histolytica. Only chloroformsoluble fraction showed 80%inhibition of trophozoites at 900 mg/kg dose. The active principle from active fraction showed 100%inhibition at 300mg/kg dose. Conclusion: Structuralmodification of the Gedunin is required for further enhace the antiamoebic activity.