A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included meta-analysis results showed that UC-MSCs can reduce mortality (relative risk RR =0.60, 95% confidence interval CI: 0.38, 0.95, P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: 0.65, 1.10, P=0.22; RR=1.00, 95%CI: 0.64, 1.58, P=1.00) addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. UC-MSCs hold promise as a safe and effective treatment for COVID-19. PROSPERO, identifier CRD42022304061.