Diabetes mellitus is a complex chronic illness characterized by the body’s inability to metabolize glucose leading to severe damage on organs such as the heart, blood vessels, kidneys, and nerves. The most prevalent type is type 2, which is due to insulin resistance coupled with progressive insulin secretory defect and is responsible for about 90% of the cases. Over six million deaths due to diabetes were reported in 2021, with Botswana diabetes-related mortality being estimated at 6%. The current synthetic therapeutics used to manage diabetes have several disadvantages, including reduction of efficacy, adverse side effects, and in some cases, liver toxicity. Therefore, this project aims to investigate the antidiabetic potential of the selected medicinal plants (Cassia abbreviata, Harpagophytum procumbens, Myrothamnus flabellifolius, Aloe zebrina, and Erythrococca trichogyne) based on the ethnomedicinal claims regarding their use to treat diabetes in Botswana. A bioassay-guided isolation approach will be used.