The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab’s safety and efficacy profile in SSc patients. A systematic online query was performed in PubMed, Scopus, Web of Science, and Embase. The studies on the application of rituximab for patients with SSc were reviewed comprehensively for over two years. In terms of efficacy profile, mRSS, MS, LVEF, sPAP, FVC, DLCO, TLC, FEV, DAS, severity activity, HAQ-DI and SF36 were assessed for organ involvement and quality of life. The level of biological and immunological markers was also evaluated in SSc patients treated with RTX. In total, 24 studies met the criteria. Although they did not have a high quality, they were free from heterogeneity and publication bias. The pooled results revealed a long-term improvement in mRSS and MS. HAQ-DI was improved to 0.78 after 12 months, and DAS was significantly reduced to 0.33, 0.23, and 0.24 following 6, 12, and 24 months of treatment, respectively (p = 0.00 for both parameters). The rest of the parameters remained stable over time in patients with SSc. The pooled analysis of these patients demonstrated that the induction of death, cancer, infection, and infusion were 9, 5, 18 and 10%, respectively. Based on the pooled results of this meta-analysis, rituximab improves skin score and disease indices and stabilizes organ involvement in SSc patients. Rituximab seems to possess reasonable safety, similar to previous data from other autoimmune diseases.