Metabolic syndrome, which includes a series of metabolic disorders such as hyperglycemia, hyperlipidemia, insulin resistance and obesity, has become a catastrophic disease worldwide. Accordingly, probiotic intervention is a new strategy to alleviate metabolic syndrome, which can adjust the gut microbiota to a certain extent. The aim of the current work was to explore the alleviation of metabolic syndrome by Lactobacillus reuteri and L. rhamnosus. Two L. reuteri and two L. rhamnosus strains were administered to mice with a high-fat diet for 12 weeks. All Lactobacillus strains tested significantly slowed weight gain in the mice. Among four strains, L. reuteri FGSZY33L6 and L. rhamnosus FJSYC4-1 showed the strongest ability to relieve blood glucose disorders, blood lipid disorders, tissue damage, and particularly gut microbiota disorders. Thus, our findings indicate that these strains can regulate the gut microbiota and produce short-chain fatty acids (SCFAs), which can induce satiety hormones, inhibit food intake and increase satiety, and thus improve metabolic syndrome.