Introduction: Traditional medicine is an ancient medical practice that is still widely used in prevention and treatment of various health problems worldwide, including Ethiopia. M.gracilipes is one of medicinal plant in Ethiopia used for treatment of various ailments still is very common. This study evaluated the sub-chronic toxic effects of M. gracilipes aqueous leaves extract on biochemical parameters and histopathology of liver and kidneys. Methods: For sub-chronic toxicity study a total of 30 mice were used, three groups (I–III) of mice (10 animals each) were used. Group I served as control and received a vehicle while groups II and III daily administered with 700 and 2100 mg/kg extract respectively orally by using oral gavage for 90 days. At the end of the experiment, the mice were sacrificed by using diethyl ether; blood was collected for assessing biochemical parameters and histopathological evaluations on liver and kidneys were performed. Results: Sub chronic treatment of extract for 90 days, at 700 and 2100 mg/kg body weight did not induce any sign of illness and /or death and had no adverse effect on biochemical parameters and blood parameters. Liver and kidney sections also revealed normal architecture, except some pyknotic nuclei and focal mononuclear leukocytic infiltrations observed in some of the liver and kidney tissues at higher dose (2100mg/kg). Conclusion: The results of this sub chronic toxicity study showed that M. gracilipes aqueous leaves extract is safe at daily doses of 700 mg/kg body weight, even when taken for longer period. At higher doses, however, the extract may induce mild hepatorenal toxicity.