The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti-diabetic-linked anti-hyperglycemia potential using in vitro biochemical assays. There was moderate-to-high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate-to-high α-glucosidase inhibitory activity. Although the anti-diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti-hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α-glucosidase and 2,2-diphenyl-1-picrylhydrazyl radical inhibitory activity indicating anti-hyperglycemia potential. Copyright © 2012 John Wiley & Sons, Ltd.