Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by established chronic inflammation. Neopterin levels have extensively been considered as a marker of immune activation during inflammation. In this study, we performed a systematic evaluation and meta-analysis to elucidate the overall relationship between neopterin concentration and RA disease activity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using PubMed, Google Scholar, Web of Science, and Scopus from 2000 to August 2020. The Newcastle-Ottawa scale was used to assess the quality of eligible studies. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to evaluate this association. A total of 15 studies out of 98 met our inclusion criteria. The pooled analysis found that patients with RA had high level of neopterin; however, no statistically significant association was found between neopterin levels with high, intermediate, and low diseases activity score (DAS)-28 (ES =11.18, 95% CI: 6.02 to 16.34, and I 2 = 91.8%; and ES = 8.57, 95% CI: 6.41 to 10.37, and I 2 = 99.5%; and ES =12.45, 95% CI: −1.68 to 26.58, and I 2 = 99.0%, respectively). Our results indicated that the neopterin concentration does not seem to have any substantial impact on the RA disease activity.