With the raising of the living standard, the number of patients with type 2 diabetes has increased year by year. It is an urgent issue that prevented and treated type 2 diabetes effectively. The aim of this study was to explore whether two probiotics, Lactobacillus rhamnosus CCFM0528 and L. plantarum X1, with an ability to alleviate type 2 diabetes, and chromium-rich yeast have synergistic effect on alleviating type 2 diabetes. The model of type 2 diabetes was induced by feeding high-fat diet and intraperitoneal injection of STZ. The fifty mice were divided into five groups: control groups, model group, drug group, probiotic group and cocktail groups. The results showed that the body weight of mice in the model group was significantly reduced, and the blood glucose increased dramatically and reached the modeling standard, indicating the model was established successfully. The blood glucose of the mice in probiotic group and the cocktail group were significantly reduced, while the hypoglycemic effect in the cocktail group was more obviously, the blood lipid level and inflammation level were alleviated in both probiotic group and cocktail group, the result indicating that probiotic and chromium-rich yeast have synergistic effect on alleviating type 2 diabetes. This study would provide a theoretical basis for the development of safe and effective probiotic combination products in alleviating type 2 diabetes.