Sodium-glucose co-transporter-2 inhibitors (SGLT2is) not only have antihyperglycemic effects and are associated with a low risk of hypoglycemia but also have protective effects in organs, including the heart and kidneys. The pathophysiology of diabetes involves chronic hyperglycemia, which causes excessive demands on pancreatic β-cells, ultimately leading to decreases in β-cell mass and function. Because SGLT2is ameliorate hyperglycemia without acting directly on β-cells, they are thought to prevent β-cell failure by reducing glucose overload in this cell type. Several studies have shown that treatment with an SGLT2i increases β-cell proliferation and/or reduces β-cell apoptosis, resulting in the preservation of β-cell mass in animal models of diabetes. In addition, many clinical trials have shown that that SGLT2is improve β-cell function in individuals with type 2 diabetes. In this review, the preclinical and clinical data regarding the effects of SGLT2is on pancreatic β-cell mass and function are summarized and the protective effect of SGLT2is in β-cells is discussed.