Restless legs syndrome (RLS) is a common complaint in patients undergoing hemodialysis (HD). Despite the fact that the estimated prevalence of RLS among HD patients is widely reported, these results varied significantly in the relevant literature. Due to this limitation, the aim of this study was to determine the global prevalence of RLS among HD patients. This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. We searched the electronic databases: Cochrane Library, PubMed, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. A random effects model was employed to calculate pooled prevalence rates. The global pooled prevalence of RLS in HD patients was 27.2% (95% CI: 24.8-29.7). Stratified analyses demonstrated that included studies with sample size <100 had the highest pooled prevalence of RLS. The prevalence of RLS using clinical interviews and questionnaires was 28.7% (95% CI: 25.2-32.2) and 25.9% (95% CI: 22.8-29.1), respectively. RLS prevalence is higher in females (29.7%, 95% CI: 26.2-33.2) HD patients than in males (23.5%, 95% CI: 20.9-26.0), and the African region has the highest prevalence in the world when the diagnostic criteria were restricted to the 2003 version of International RLS Study Group criteria, the prevalence of RLS was highest (28.9%, 95% CI: 25.9-31.9). Our results revealed a high RLS prevalence in HD patients worldwide. However, the prevalence of RLS among HD patients varied significantly based on sample size, data collection method, gender, diagnostic criteria, and geographical region.