Gynostemma pentaphyllum (GP) is a natural plant resources for diabetes therapy, however, there is little research on the mechanisms of GP. The present study was undertaken to characterize if G. pentaphyllum saponins (GPs) is the principal active compound of GP responsible for anti-diabetes, and to examine the relativity between blood glucose modulate and antioxidation. The GPs-treated streptozotocin diabetic rats had a more effective hypoglycemic status than those of diabetic control rats, which also ameliorate dyslipidemia. GPs has increased SOD and GSH-px activities, and the spleen and thymus indexes in diabetic rats. The insulin levels in the GPs-treated groups were significantly higher than diabetic control group. Our finding provides a new insight into the application of GPs for the treatment of oxidative stress related diseases.