Doctoral Degree. University of KwaZulu-Natal, Durban.The present study investigated the effects of five African medicinal plants (Alstonia boonei, Acalypha wilkesiana, Boerhaavia diffusa, Bridelia ferruginea, and Crassocephalum rubens) for their antioxidative and antidiabetic potentials by using several experimental protocols. The crude extracts (ethyl acetate, ethanol and aqueous) of the different parts (leaves, stem bark, root bark or aerial parts when applicable) were initially investigated for their detailed antioxidant and antidiabetic activity using in vitro, ex vivo and in silico experimental models. Then the most active crude extract from each plant was chosen for further fractionation with the solvents of increasing polarity. The solvent obtained fractions were then subjected to screening in terms of their antioxidant, -glucosidase, -amylase and lipase inhibitory activity in vitro and intestinal glucose absorption and muscle glucose uptake ex vivo. Results from these assays revealed that the butanol and aqueous fractions of A. boonei, butanol fraction of B. ferruginea, ethanol extract of A. wilkesiana and B. diffusa and the aqueous extracts of C. rubens showed the best activities in terms of all the tested models. The most active crude extracts and fractions were consequently subjected to GC-MS and LC-MS analyses in order to identify their bioactive components. Then the structures of the most bioactive components were docked with the tested enzymes using in silico modelling. The anti-diabetic effect of the butanol fractions of A. boonei and B. ferruginea together with the aqueous extract of C. rubens were investigated in an in vivo intervention trial using a type 2 diabetes rat model. The in vivo experiment revealed that the fractions and extract exhibited potent in vivo hypoglycaemic activity. Interestingly, these fractions were also able to alleviate T2D-associated complications involving oxidative stress. Analysis of in vivo oxidative stress markers such as superoxide dismutase, catalase, glutathione and thiobarbituric acid reactive substances, in the serum, liver, kidney, heart and pancreas of the animals also suggested their strong antioxidative effects. The results of this study suggest that the different extracts/fractions of the above-mentioned plants have promising anti-diabetic potentials; however further clinical trials are required in order to justify the usefulness of these plants for the development of potent and cost effective anti-diabetic drugs