In recent years, the introduction of sodium-glucose transporter-2 inhibitors (SGLT2is) marked a significant advancement in the treatment of cardiovascular disease (CVD). Beyond their known effects on glycemic control and lipid profile, SGLT2is demonstrate notable benefits for cardiovascular morbidity and mortality, regardless of diabetic status. These agents are currently recommended as first-line therapies in patients with heart failure, both with reduced and preserved ejection fraction, as they improve symptoms and reduce the risk of hospitalization. While several studies have demonstrated that SGLT2is can reduce the incidence of major adverse cardiovascular events (MACEs), the true impact of these agents on atherosclerosis progression and myocardial ischemia remains to be fully understood. A global beneficial effect related to improved glycemic and lipid control could be hypothesized, even though substantial evidence shows a direct impact on molecular pathways that enhance endothelial function, exhibit anti-inflammatory properties, and provide myocardial protection. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs in preventing and treating myocardial ischemia, aiming to define an additional area of application beyond glycemic control and heart failure.