The current systematic review and meta-analysis aims to evaluate the efficacy and safety of iguratimod (IGU) combined with methotrexate (MTX) versus MTX alone in rheumatoid arthritis (RA). Two independent investigators searched for original randomized controlled trials (RCTs) related to the combination of IGU and MTX in RA published before November 1, 2019, in PubMed, Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), and WanFang Data. Additionally, we searched clinical trial registry websites. We assessed the methodological quality of the included trials using the Cochrane Collaboration tool and the seven-point Jadad scale. Statistical analyses were performed using Review Manager (RevMan) 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Meta-regression and publication bias analyses were performed using Stata version 14 software (StataCorp., College Station, TX, USA). A total of 7 RCTs consisting of 665 participants, with 368 participants in the active arm and 297 in the placebo arm, were included in the meta-analysis. The American College of Rheumatology (ACR) value was better in the IGU + MTX group than in the MTX alone group, with a pooled relative risk (RR) for ACR20 (American College of Rheumatology 20% improvement criteria), ACR50, and ACR70 of 1.40 (95% CI, 1.13–1.74), 2.09 (95% CI, 1.67–2.61), and 2.24 (95% CI, 1.53–3.28), respectively. The results of the meta-analysis demonstrated that there was no statistical significance in adverse events (1.06 (95% CI, 0.92–1.23)). The combined treatment is an effective, safe, and economical treatment option for patients who do not respond well to methotrexate alone or for patients who cannot afford expensive biologics that have no confirmed efficacy.