Background:Diabetic nephropathy (DN) is a common cause of end-stage renal disease (ESRD). The benefits and effects of renin–angiotensin system blocker drugs are obvious in decreasing albuminuria, but there is a need to find other drugs that can decrease albuminuria. The aim of our study is to evaluate the effect of short-term administration of curcumin on overt albuminuria in patients with type 2 diabetes mellitus (T2DM).Materials and Methods:A randomized, double-blind clinical trial was performed on 46 patients with T2DM, overt albuminuria ≥300 mg/24 h, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. After the random allocation of the patients, they were divided into two groups. In the curcumin group, the patients received 500 mg (one capsule) of curcumin with each meal (three times/day after meal) for 16 weeks. Other variables including blood urea nitrogen (BUN), creatinine (Cr), fasting blood sugar (FBS), 2-h postprandial blood sugar (2-h pp BS), lipid profile, 24-h urine analysis for albuminuria, serum albumin, and hemoglobin A1C (HbA1C) were checked at baseline and bimonthly too.Results:two groups at baseline were comparable in terms of basic characteristics (P > 0.05). Albuminuria decreased significantly from 900.42 ± 621.91 at the baseline to 539.68 ± 375.16 at the end of the study in the curcumin group (PTime = 0.002); however, no statistically significant changes were observed in the placebo group (519.94 ± 214.33 at the baseline vs. 444.00 ± 219.10 at the end of the trial; PTime = 0.43), and the decrease was significantly higher in the curcumin group than that of the placebo group (PIntervention = 0.01). No significant differences were observed between the placebo and curcumin in terms of changes in serum BUN, Cr, FBS, 2-h pp BS, HbA1C, lipid profile, and albumin.Conclusion:Our study showed that curcumin as an active turmeric metabolite was an effective adjuvant therapy for ameliorating macroscopic proteinuria in type 2 diabetic patients. Its effect may appear after 2 months of therapy and even in patients with a mild decrease in GFR. Further studies with larger sample size and longer duration are recommended.