Cyphostemma setosum is a traditional medicinal climber, distributed in Palani hills, the Western Ghats, Tamil Nadu, India. In this region, the puliah tribal community is using this species more commonly to control type II diabetics. As there is no work in this line, the present study was carried to investigate the in vitro antidiabetic activity of C. setosum in terms of the level of inhibition of α-amylase and α-glucosidase as influenced by methanolic extract of aerial parts of this species. The results showed that the extract inhibits the α-amylase and α-glucosidase enzymes very considerably and also exhibited the IC50 values 123.11±2.34 and 279.69±4.21µg/mL respectively. The study evidenced strongly that the probable inhibition of these two enzymes may lowers the blood glucose levels. Thus this species, C. setosum is claimed to have antidiabetic activity and further studies on in vivo models are in most needed.