Euonymus alatus (EA), known as a Gui Jeon Wu in China, has been used as a folk medicine for regulating blood circulation, relieving pain, eliminating blood clot, and treating dysmenorrhea in Asian countries. Although EA has anecdotally ascertained to show the anti-hyperglycemic activity by enhancing insulin secretion, there is no sufficient experimental evidence for anti-hyperglycemic activity of EA. The purpose of this study was to investigate the preventive effect of 50% ethanol extract of EA in high-fat diet-induced hyperglycemic and hyperlipidemic ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice was to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high-fat diet with either 350, 700 mg/kg of EA (EA350 and EA700) or 250 mg/kg of metformin (MET250) for a 10-week period. EA not only reduced body weight in a dose dependent manner, but also corrected associated hyperinsulinemia and hyperlipidemia. EA exerted beneficial effects on glucose and lipid homeostasis in diabetes that are not secondary to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBPla, FAS, GAPT) and PPAR-gamma gene expression in periepididymal fat. Taken together, the combined effect of EA to reduce plasma glucose and lipid levels, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related diabetes and non-alcoholic fatty liver disease.