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Objective Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism. Methods All articles published until the end of 2016 in PubMed that dealt with the relationship of antidiabetic drugs and the kidney were reviewed and the relevant information is presented here. Results In this review, we summarize the available evidence on the drugs that act through the inhibition of renal glucose reabsorption, discuss the adjustments in the dose of antidiabetic drugs in patients with various stages of kidney disease and explore the renoprotective potency of the various glucose-lowering compounds. Conclusion Sodium glucose cotransporter 2 inhibitors represent a very promising option for the treatment of type 2 diabetes, especially in patients with established cardiovascular disease. These drugs, along with pioglitazone and incretin mimetics may also reduce the incidence and the rate of progression of diabetic nephropathy.