The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption—resulting in glycosuria—and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.