Salacia oblonga is used to treat diabetes, hypocholesteremia, gonorrhea, rheumatism, asthma, inflammation, oxidative stress, etc. In the present study, the antidiabetic activity of S. oblonga methanolic root extracts collected from three geographical locations, viz., Eleshwaram (Andhra Pradesh), Thoothukudi (Tamil Nadu), and Karwar (Karnataka), was studied in vitro. Among the three extracts, S. oblonga root extracts from Eleshwaram showed maximum α-glucosidase and α-amylase inhibitory activities, indicating better antidiabetic activity. Acute toxicity studies of S. oblonga carried out in Albino Wistar rats showed no toxicity. Further, in vivo studies showed antidiabetic and antilipidemic activities in Albino Wistar rats with induced type II diabetes mellitus. Type II diabetes mellitus was induced in the experimental rats by intraperitoneal injection of nicotinamide and streptozotocin. The rats were orally fed different doses (ranging from 0 to 400 mg/kg body weight) of S. oblonga root extracts from Eleshwaram for 14 days. Blood glucose, lipid, bilirubin, and creatinine levels were analyzed on day 0, 7, and 14. The S. oblonga root extract from Eleshwaram decreased the glucose levels in a dose-dependent manner as well as the lipid, creatinine, and bilirubin levels in diabetic rats. Thus, the present study demonstrates antidiabetic and antilipidemic properties of S. oblonga root extracts.