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The antidiabetic activity of saponins extracted from Momordica charantia (MCS) on streptozotocin‐induced diabetic mice was investigated in order to elucidate the mechanism of MCS for exerting hypoglycemic effects. Saponins were first extracted from M. charantia L. and their composition was analyzed. The diabetic Kunming mice were fed low‐dose saponins from M. charantia L. and high‐dose MCS, using normal mice and diabetic mice as controls. Body weight, blood glucose level, oral glucose tolerance, serum C‐peptide level, hepatic antioxidant capacity, hepatic glycogen and hexokinase in liver tissues, serum blood lipid level, and alpha‐glucosidase activity in small intestines were measured, and microstructure of pancreatic islet was analyzed. The results showed that the total content of seven triterpenoid compounds in MCS was 18.24 μg/mg, with Momordicoside K having the highest content at 11.66 μg/mg. Diabetic mice treated with MCS at 100 and 200 mg/kg body weight daily for 30 days showed a maximum glucose reduction (p <.05) of 12.63% and 26.47%, respectively. MCS significantly decreased levels of postprandial hyperglycemia, serum lipid, α‐glucosidase activity, and liver malondialdehyde. Additionally, levels of serum C‐peptide and liver glycogen, as well as hexokinase and antioxidant enzyme activity, were significantly increased compared to the diabetic control groups. Histopathological results showed that MCS markedly reduced degenerative changes in islet β‐cells. It is concluded that MCS exerts antidiabetic effects by improved hypoglycemic, hypolipidemic, and antioxidant effects, increased hexokinase activity and glycogen synthesis, and enhanced reparative effects on the histological architecture and insulin secretion function of the pancreas. [ABSTRACT FROM AUTHOR]