The hypoglycemic effect of total flavonoids extracted from citrus peels on diabetic white mice induced by alloxan was studied and the preliminary mechanism was discussed. Results showed that after intragastric administration of middle and high dosage of total flavonoids extracted from citrus peels for 10 days, the concentration of blood glucose of alloxan-induced diabetic mice reduced obviously. Compared with the model group, the spleen index, thymus gland index, and the activity of superoxides dismutase (SOD) in blood and liver of the diabetic mice were increased and the formation of the malondialdehyde (MDA) were inhibited. The contents of TG, TC, and LDL-C decreased greatly, while the content of HDL-C increased obviously. The results suggested that the improvement of immunity, antioxidation, and regulation of lipid metabolism disorders in alloxan-induced diabetic white mice may be one of the hypoglycemic mechanisms of total flavonoids extracted from citrus peels, which provided a theoretical basis to the development and utilization of citrus peels.