Abstract : The purpose of this systematic review is to compare the safety and efficacy of the cyclosporine and mycophenolate mofetil in patients with diabetes and renal failure. There is no work we found that compares the safety and efficacy of cyclosporine and mycophenolate in diabetic and renal failure patients. The search was limited from 1983 to 2017 and articles must be in English. Articles searched from various resources and are evaluated using PRISMA. 25 articles picked and screened at the end of 12 articles included in the study. The result shows that the pharmacokinetics of cyclosporine is affected by the renal failure and diabetes and mycophenolate did not show much variation in pharmacokinetics. The safety of mycophenolate in renal patients in terms of serum Creatinine is more than the cyclosporine and shifting of the patient from cyclosporine to mycophenolate shows better results. It is concluded that mycophenolate is more safe and efficacious than cyclosporine in diabetic patients with renal failure