Recent trends in diabetes treatments show an increasing interest in traditional systems of medicine. Ayurveda, a traditional Indian system medicine, advocates a wide range of medicinal plants to treat diabetes. Although there have been numerous studies on extracts from these medicinal plants that demonstrate antidiabetic activity, scientific studies directed to the isolation, purification and identification of active ingredients responsible for the hypoglycemic activity and also the modes of action of these extracts/active ingredient(s) on glucose homeostasis have been often inconclusive or lacking except for a few cases. The aim of this present study was to identify and isolate a potent antidiabetic compound(s) from some extensively advocated Ayurvedic antidiabetic plants such as 'Trigonella foenum-graecum' Linn (TFG), 'Pterocarpus marsupium' Roxb (PM), 'Gymnema sylvestre' R.Br (GS) and 'Curcuma longa' Linn (CL). An in-house developed 'in vitro' tissue culture-based bioassay method was employed in the present study to determine the effects of plant extracts on insulin secretion from mouse pancreas tissues and on glucose uptake by mouse skeletal muscle tissues under both normoglycemic (5mM glucose) and hyperglycemic (12mM glucose) culture conditions. The results from our preliminary study indicated that all these plant extracts have beneficial effects on glucose homeostasis either by stimulating insulin or enhancing glucose uptake or activating both. In terms of their comparative effects on tissues that regulate glucose metabolism, the aqueous extracts of plants, PM and CL, were found to be more potent when compared with other studied aqueous extracts of plants TFG and and GS, within culture conditions.