Background: This study aims to investigate the effect of antioxidants supplement on clinical outcomes and antioxidant parameters in rheumatoid arthritis (RA). Methods: The pre-post study was conducted on 40 female patients with RA in 12 weeks that taken daily one "Selenplus" capsule contained 50 μg selenium, 8 mg zinc, 400 μg vitamin A, 125 mg vitamin C, and 40 mg vitamin E. About 5 mL venous blood sample was taken from all participants and disease activity score (DAS) was determined by DAS-28 formula and high-sensitive C-reactive protein (hs-CRP). Glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured by spectrophotometric kit and catalase (CAT) was measured by Abei method. Total antioxidant capacity (TAC) was determined by spectrophotometric kit. Distribution of the variables was assessed using histogram with normal curve as well as Kolmogorov-Smirnov test and data were analyzed with paired t-test for differences between pre-post data using SPSS software version 13.5. Results: Out of 40 patients, 39 completed the study. DAS-28 score and hs-CRP have changed (P < 0.01 for both), while the number of swollen and painful joints did not reduce significantly. TAC, GPX, SOD, and CAT increased significantly (P < 0.01 for all variables). Conclusions: Our findings showed that antioxidants may improve disease activity significantly, but it did not affect the number of painful and swollen joints and increased erythrocyte antioxidant levels. Antioxidants may be useful for controlling of clinical outcomes and oxidative stress in RA.