Glucose spikes after meals induce endothelial dysfunction, which may lead to progression of atherosclerosis and cardiovascular events. Controlling postprandial hyperglycemia should be the potential target for preventing cardiovascular events. In clinical settings, the α-glucosidase inhibitors (α-GIs) glinides are often prescribed to prevent postprandial hyperglycemia. Recent studies have showed that α-GIs may have incretin-like effects and other pleiotropic effects. This review will describe the endothelial function associated with postprandial hyperglycemia, and will discuss the effects of α-GIs on preventing cardiovascular disease.