Diabetes mellitus has been a menace to mankind from time immemorial. However, a natural product such asU. chamaeP. Beauv (Annonaceae) offers alternative treatment for diabetes mellitus. The study aimed at evaluating antidiabetic activity of the ethanolic root extract ofU. chamaein alloxan-induced diabetic rats. Diabetes was induced in Sprague Dawley rats after overnight fast with 150 mg/kg alloxan intraperitoneally. After 72 h, those with plasma glucose levels >200 mg/dl were classified as diabetic. Five diabetic rats in each group were treated daily for 14 days orally with 100, 250, and 400 mg/kg of the extract, glibenclamide (71 µg/kg) and pioglitazone (429 µg/kg), respectively, while another group was untreated. Control received 0.5 ml ofAcacia senegal. Effects of extract on glucose, other biochemical, and hematological parameters were evaluated.α-amylase andα-glucosidase inhibitory activities of extract and its fractions were also evaluated. Percentage inhibition and IC50values were determined. Diabetic control was achieved on the 7th day of the study with 100, 250, and 400 mg/kg of the extract showing glucose reduction of 72.14%, 78.75%, and 87.71%, respectively. The HDL-cholesterol levels of diabetic rats treated with extracts were significantly increased. Extract and its fractions causedα-amylase andα-glucosidase inhibition. Histologically, pancreas of diabetic rats treated with extract showed regenerated islet cells which were not seen in rats treated with glibenclamide and pioglitazone. This study showed thatU. chamaehas antidiabetic activity which may be throughα-amylase andα-glucosidase inhibition and regeneration of pancreatic beta cells. Also, it may reduce the risk of cardiovascular disease by increasing HDL-cholesterol levels.