This work investigated the acute and subchronic toxicity profile of aqeous stem bark and leaf extract of Costus afer ker (Zingiberaceae). This plant is used extensively for food, economic, and medicinal purposes in Nigeria. Acute oral toxicity studies in male and female mice did not produce any sign of acute toxicity or death even at the dose of 4,000 mg/kg. Thirty-six albnino Wistar mice of varied sexes weighing between 28 and 35 g were divided into four groups. Groups A, B, and C were given different concentrations of the extract at 20, 13.33, and 6.67 mg/ml, respectively in water. Group D served as the control and was given only water. The experiment lasted for a period of 56 days. The packed cell volume, hemoglobin concentration, and the total red blood cell count decreased significantly (p < 0.05) in comparison with the control. Serum biochemistry showed no significant changes in the activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase when compared with the control. The histopathological studies revealed no significant lesions in the heart, kidney, and liver. There was also no significant chages in weight between the experimental animals and the control.