This article reviews the multifaceted benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors beyond their traditional role in glycemic control. A comprehensive systematic literature review was conducted, covering 26 randomized controlled trials (RCTs) involving 35,317 participants from 2000 to 2024. The findings highlight that SGLT2 inhibitors not only enhance metabolic control but also provide significant cardioprotective and renoprotective effects. Specifically, they reduce cardiovascular death and hospitalization for heart failure (HF), slow the progression of chronic kidney disease (CKD), and decrease albuminuria. These benefits are observed in both diabetic and nondiabetic individuals, with acceptable safety profiles. The review also discusses the biological plausibility and underlying mechanisms, emphasizing the potential of SGLT2 inhibitors in addressing cardiac, renal, and metabolic conditions in nondiabetic patients. However, further research is needed to fully elucidate the mechanisms and long-term outcomes associated with their use in nondiabetic populations.This article reviews the multifaceted benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors beyond their traditional role in glycemic control. A comprehensive systematic literature review was conducted, covering 26 randomized controlled trials (RCTs) involving 35,317 participants from 2000 to 2024. The findings highlight that SGLT2 inhibitors not only enhance metabolic control but also provide significant cardioprotective and renoprotective effects. Specifically, they reduce cardiovascular death and hospitalization for heart failure (HF), slow the progression of chronic kidney disease (CKD), and decrease albuminuria. These benefits are observed in both diabetic and nondiabetic individuals, with acceptable safety profiles. The review also discusses the biological plausibility and underlying mechanisms, emphasizing the potential of SGLT2 inhibitors in addressing cardiac, renal, and metabolic conditions in nondiabetic patients. However, further research is needed to fully elucidate the mechanisms and long-term outcomes associated with their use in nondiabetic populations.