According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbAlevels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists.