Abstract Background and Objective: Incomprehensive studies have examined the therapeutic and side effects of curcumin on the treatment of debilitating diseases, such as Rheumatoid Arthritis (RA). This study aimed to explore the anti-inflammatory effects of curcumin on RA.Materials and Methods: This double-blind clinical trial was carried out on 64 RA patients with an erythrocyte sedimentation rate (ESR)-Disease Activity Score (DAS)-28>2.6. The patients were then randomly divided into two groups of intervention and control. In addition to the routine treatment, the intervention group was treated with 80-mg/day capsules of curcumin (nano-micelles). Further, the patients were followed up for three months, and clinical-laboratory examinations were recorded in this study.Results: There was no significant difference between the intervention and control groups regarding the trends of the disease activity indicators, including DAS-28, disability index, physician assessment, and the number of tender joints (P>0.05). Further, a significant difference was found between the two groups in terms of pain score changes and the number of swollen joints. Additionally, the curcumin-treated subjects obtained lower mean pain and fewer swollen joints, compared to those in the control group (P<0.05).Conclusion: The present study revealed that curcumin had no significant therapeutic effects on reducing the activity of RA; however, no significant side effects were observed on the patients, and it also showed its analgesic effect well. Keywords: Curcumin, Disability, ESR-DAS-28, Rheumatoid Arthritis, Clinical Trial, Anti-Inflammatory Effects