Diabetes mellitus (DM) is a serious metabolic disorder affecting about 425 million people worldwide with estimated 2.2 million deaths annually. The management of diabetes mellitus by the use of orthodox medicines has been unsatisfactory with huge financial burden to the patients in addition to the associated side effects. Therefore, the search for affordable, relatively safe and sustainable materials as alternative to synthetic drugs is inevitable. In this study, seeds of Telfairia occidentalis, a vegetable plant widely consumed in most part of Nigeria was evaluated for its in vivo inhibitory role on alpha amylase and alpha glucosidase enzymes in rats. The seed extracts (150, 300 and 450 mg/kg) were investigated using starch, sucrose, and maltose as substrates and acarbose as reference drug. The seed extract caused significant (p<0.05) reduction in blood glucose levels of the treated rats with the various substrates used. Preliminary phytochemical screening of the seed extract showed that alkaloids, flavonoids, saponins, cardiac glycosides, anthraquinones and tannins were present. The findings show that the seed extract of Telfaira occidentalis has inhibitory effects on alpha amylase and glucosidase in rats which, may be attributed to the presence of the phytochemical compounds