Background: Low-dose interleukin-2 (IL-2) shows promise as a treatment for restoring functional and numerical deficits of regulatory T (Treg) cells in patients with various autoimmune diseases. Several clinical trials testing low-dose IL-2 in systemic lupus erythematosus (SLE) have been completed, with a comprehensive review of these trials currently lacking. Objective: We aimed to conduct a systematic synthesis and meta-analysis of findings from clinical tri-als regarding the clinical efficacy and safety of using low-dose IL-2 in patients with SLE. Furthermore, we intended to determine the sensitivity of different responder indexes for IL-2-induced clinical im-provement in SLE. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched the Scopus and MEDLINE databases for articles reporting trials testing low-dose IL-2 in pa-tients with SLE published between January 2010 and September 2022. For assessment of the risk of bias, we used a modified Downs and Black assessment. Results: We retrieved 1,018 articles, six of which we analyzed including four open-label studies and two randomized controlled trials following a detailed review process. The studies included a total of 230 patients, of which 150 received low dose IL-2 and 80 received placebo. Although the open-label studies demonstrated an expansion of Treg cells that coincided with a clinical response, the primary endpoints for clinical efficacy were not achieved in the randomized controlled trials. In general, treat-ment with low-dose IL-2 appears to be safe and tolerated well. Conclusion: Low-dose IL-2 therapy seems to be an attractive approach to treating SLE, although larger trials investigating clinical responses in patients with such a heterogeneous disease remain needed.