Traditional medicinal plants are a worthy source of secondary metabolites (alkaloids, terpenoids, phenolics, flavones and polyphenols) which play a vital role in the defence mechanisms of the host against pests and microbes. However, these secondary metabolites have been shown to possess potential antidiabetic, antioxidant, immunomodulatory, anti-asthmatic and anti-inflammatory activities. This research investigated the in vitro and in vivo effects of five traditionally used antidiabetic plants for insulinotropic and hyperglycaemic potential. Extracts (hot water and ethanol) of medicinal plants (A. squamosa, C. sinensis, E. citriodora, A. arabica and H. fomes) stimulated concentration-dependent insulin release from rat clonal BRIN BD11 cells and isolated mouse islets. Non-toxic concentrations of extracts further enhanced the insulinreleasing actions of glucose, tolbutamide, IBMX and KCl. Insulin secretory effects were partially reduced by diazoxide, verapamil and under calcium-free conditions, being associated with membrane depolarization and increased intracellular Ca2+ . Extracts also increased glucose uptake/insulin action in 3T3L1 adipocyte cells and inhibited protein glycation, DPP-IV enzyme activity, starch digestion and glucose diffusion. Acute administration of plants to high-fat fed (HFF) rats improved glucose tolerance, plasma insulin and inhibited plasma DPP-IV enzyme activity. These results encouraged longterm follow up studies, where plants induced remarkable benefical changes in HFF rats of non-fasting blood glucose, glucose tolerance, plasma insulin and DPP-IV, body weight, food consumption, fluid intake, pancreatic insulin content and the islet, beta cell and alpha cell areas. A. squamosa significantly increased unabsorbed sucrose content and reduced both postprandial hyperglycaemia and glucose absorption during in situ gut perfusion. The compounds isolated from plants: rutin from A. squamosa and C. sinensis, isoquercitrin from C. sinensis and E. citriodora, quercetin from A. arabica and, quercitrin from H. fomes and E. citriodora also induced concentration-dependent insulin secretion in vitro and enhanced glucose tolerance and plasma insulin in Swiss albino mice. In conclusion, this research demonstrates the potential of traditionally used antidiabetic plants and their active constituents to modulate multiple signalling pathways that result in significant antidiabetic activities. Such plants may provide important dietary adjuncts for treatment of diabetes and offer a valuable source of new drugs for the prevention, treatment and management of the disease.