Sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed the treatment of both cardiovascular and renal diseases. Although originally developed for glycemic control in type 2 diabetes mellitus, these agents have demonstrated significant benefits by reducing cardiovascular events and slowing the progression of kidney disease, even in patients without diabetes. Landmark trials, including EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, and DAPA-HF, consistently demonstrated reductions in heart failure hospitalizations and renal deterioration among patients at high cardiovascular risk. However, many of these studies excluded patients with advanced chronic kidney disease (CKD), limiting the generalizability of their findings for this population. More recent investigations, such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have focused on patients with CKD and confirmed that SGLT2 inhibitors offer significant renal and cardiovascular protection regardless of diabetic status. This review summarizes key clinical trials, outlining their design and outcomes with a particular emphasis on inclusion and exclusion criteria and the implications for CKD populations. Further, it discusses the practical application and safety considerations of SGLT2 inhibitors in nephrology, underscoring their emerging role as a fundamental therapeutic strategy in CKD management.