Background: Diabetic nephropathy (DN) is considered a severe disorder which affects health worldwide. New more active treatment options are required. Despite a large number of drugs already being available for treatment of hyperglycemia in diabetes, current oral antidiabetic agents often do not provide adequate glycemic control. Renin-angiotensin-aldosterone system (RAAS) blockers are novel agents to slow the progression of DN. Method: The present review provides an overview of recent studies on DN management, especially the use RAAS blockers and their antidiabetic effects. References were mainly identified through PubMed search until December 2016 and backtracking of references in pertinent studies. Results: This review reporting the novel mechanisms and benefits of targeting the RAAS by the use of ACEIs; ARB or direct renin inhibitors in glucose lowering, antioxidant and anti-inflammatory effects and kidney protection. Conclusion: These drugs targeting the RAAS can be used as monotherapy or in combination therapy in hypertensive-diabetic patients to protect them from DN.