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Woretaw Sisay, Yared Andargie, Mulugeta Molla Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, EthiopiaCorrespondence: Woretaw Sisay, Email sisayworetaw@gmail.com; woresis@dtu.edu.etBackground: Despite modern therapeutic armamentaria, DM remains a 21st-century public health menace. Novel phytomedicines are a rapidly expanding focus of research. The juice of Dorstenia barnimiana roots has long been used for the treatment of diabetes mellitus in traditional Ethiopian medicine, but its efficacy has not been supported by in vitro or in vivo scientific study. To investigate this, the present work was performed.Methods: In this experimental study, simple random sampling was applied. Healthy male mice were used in normoglycemic and oral glucose-tolerance test (OGTT) models. Streptozotocin (IP, 150 mg/kg)–administered diabetic male mice were utilized. Animals were randomly divided into five groups of six each. Group I received 10 mL/kg distilled water, groups II–IV received 100 (DB100), 200 (DB200), and 400 (DB400) mg/kg crude extract, respectively, and group V received glibenclamide 5 mg/kg. A sham group (group VI) was added that received 10 mL/kg distilled water. All treatments were given orally. FBG, serum-lipid profiles, and body-weight changes were then measured. In vitro α-amylase inhibitory activity was also evaluated.Results: The doses were atoxic up to 2,000 mg/kg. There was α-amylase inhibition activity of 67.52% at 500 μg/mL with an IC50 of 4.595 μg/mL. The OGTT revealed an antihyperglycemic effect of the crude extract. This was not attributed to a hypoglycemic side effect. In the diabetic mouse model, it shrank FBG levels remarkably. There were also significant reductions in serum TC, TGs, VLDL-C, and LDL-C. Nevertheless, HDL-C and body-weight levels returned.Conclusion: The present study confirmed the safety and promising in vivo antidiabetic and antidyslipidemic activity of D. barnimiana, thus corroborating the t