Diabetes can have several mac-rovascular and microvascular complications in addition to diabetic nephropathy, also referred to as diabetic kidney disease (DKD). DKD is found to occur in approximately 40% of patients with type 2 diabetes and 30% of patients with type 1 diabetes. However, research on the ef-fects of antihyperglycemic agents on the renal outcomes of these patients is still in its infancy. The current review explores glycemic manage-ment in patients with DKD, focusing on the chal-lenges faced as well as the clinical consider-ations of antihyperglycemic agents in this pop-ulation. A comprehensive literature review was conducted using EMBASE, Web of Science, and PubMed databases. This review was complet-ed by the end of March 2023, and the following keywords were used for the search: diabetic ne-phropathy, diabetic kidney disease, safety, effi- cacy, and antihyperglycemic therapies. The sev-eral concerns about the use of antihyperglyce-mic agents in treating diabetes in patients with DKD highlight the need for substantial efforts in educating both patients and healthcare practi-tioners in this regard. In addition, it is suggested that patients receive individualized treatments, considering the potential long-term benefits of each agent; this would entail prospectively mod-ifying doses in line with the stage of DKD to pre-vent the progression of renal damage. As some classes of agents offer better renoprotective ef-fects for patients with DKD, it would be wise for nephrologists and endocrinologists to collab-orate to offer an antihyperglycemic regime for patients with DKD who are at a high risk of fur-ther progression. Further study is needed on the beneficial renal effects of specific class- es of agents; more knowledge of their mecha-nisms and renoprotective effects may contrib-ute to the development of novel treatments for patients with DKD.