Abstract: Many plant based medicines used since time immemorial have never undergone vigorous scientific testing, despite countless reports on cases of health hazards arising from their unbridled usage. In light of this, since recent research has unearthed a novel anticoagulant property present in the Melastoma malabathricum leaf extract, this study evaluated its subacute safety profile. Sprague-Dawley rats of both sexes were orally administered with deionized water (vehicle control), 50, 75 and 100 mg kg-1 aqueous leaf extract daily for 28 days. At day 29, all animals were scarified. Blood samples were collected and analyzed blood biochemical enzymes; while, organs were harvested, weighed and subjected to tissues histopathological examination. There were no aberrant physical and behavioral changes in the treated rats. However, blood chemistry analysis revealed significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. Correspondingly, histopathology of liver and kidney tissues showed extensive toxic manifestations. All hepatic venous structures appeared dilated and congested. Tissue hemorrhage and tubular damage were seen in the kidneys. These results collectively highlight the predisposition of Melastoma extract to be hepato- and nephrotoxic if taken repeatedly via oral route for a long period. This is the first exploratory study on the nature of Melastoma leaf’s aqueous extract subacute oral toxicity.