This study investigated the effects of Gymnema sylvestre (GS) extract on body weight, adiposity, and lipid metabolism in leptin-deficient ob/ob mice. The experimental mice were divided into the following 4 groups: basal diet (AIN-93G diet) and 0.5%, 1%, and 1.5% GS supplemented groups. Each group was fed the experimental diet for 9 weeks. The final body weights, adipocyte sizes, and epididymal fat weights of the GS groups were significantly lower than those of the control group. There were no significant differences in food intake and food efficiency ratios among the treated groups. Serum triglyceride levels and the atherogenic index were significantly lower in the GS groups compared to the control group. Serum HDL cholesterol levels were significantly higher in the 1% and 1.5% GS groups compared to the control group. Serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities did not differ among the four experimental groups. The total hepatic lipid content was significantly lower in the GS groups, and hepatic cholesterol and triglyceride contents tended to be reduced in the GS groups compared to the control group. These results suggest that GS extract may be useful for ameliorating dyslipidemia and fatty liver.