Acanthamoeba is an opportunistic pathogen causing keratitis and fatal encephalitis. Early diagnosis, followed by intense treatment using a drugs mixture is a necessity for effective therapy. Many natural compounds have proved lethal effects, yet the search for original natural amebicidal agents is still of current concern. This study investigated the acanthamoebicidal effect of A. hypogaea L. pericarp; total ethanol extract and its successive fractions, n-hexane, dichloro-methane, ethyl acetate, and methanol as well as resveratrol. Acanthamoebae were isolated and cultivated on E. coli seeded nonnutrient agar, genotyped, and the in vitro acanthamoebicidal potentials of different concentrations of A. hypogaea L. pericarp; total extract ethanol and its successive fractions and resveratrol compound was investgated on cysts of A. astronyxis T7 genotype. The results showed variable degrees of lethal potentials were obtained by all examined A. hypogaea L. pericarp ethanol extract and its successive fractions, with the highest mean of non-viable cysts on the first and the second days of the study by total ethanol extract followed by the methanol fraction . On the third day of the study n-hexane and ethyl acetate gave the highest mean of non-viable cysts. Resveratrol showed the lowest mean of non-viable cysts count all through the study duration. Significantly higher difference was observed between all examined A. hypogaea L. pericarp extract and fractions and chlorohexidine, except for resveratrol compound the difference was found to be non-significant.