BACKGROUND: Ulcerative colitis (UC) in pediatric patients often results in corticosteroid (CS) dependency, with many individuals developing resistance to conventional treatments such as anti-TNF agents. Vedolizumab, a monoclonal antibody targeting α4β7 integrin, has shown promise in adult populations, but data on its efficacy and safety in children and adolescents are limited. OBJECTIVES: This systematic review aims to assess the effectiveness and safety of vedolizumab in treating UC in pediatric patients. DESIGN DATA SOURCES AND METHODS: The PRISMA statement's guidelines were followed in conducting this systematic review. Up until December 2024, a thorough search was carried out using keywords associated with inflammatory bowel disease (IBD), vedolizumab, and pediatric populations in the Cochrane Library, EMBASE, and PubMed. Case series of children and adolescents (less than 18 years old) with UC or unclassified IBD who were treated with vedolizumab were included in the research. Data on clinical response, mucosal healing, corticosteroid-free remission, clinical remission, and adverse events were extracted. Descriptive statistics were used in the statistical analysis. RESULTS: A total of 14 papers were considered in the current evaluation of the effectiveness and safety of vedolizumab. Nearly one-third (36%) of patients with UC/IBD-U experienced clinical remission at 6 weeks, half of the patients at 14 weeks (50%), and 48% and 53% of patients at 22 weeks, respectively. Forty-five percent of patients maintained clinical remission after 1 year. Less than 8% of UC/IBD-U patients experienced serious side effects, while 15%-34% of patients experienced mucosal healing. CONCLUSION: Vedolizumab exhibits promising efficacy and a favorable safety profile in treating pediatric UC, with a sizable portion of patients achieving both clinical and corticosteroid-free remission. However, due to the limited sample sizes and lack of investigations, more randomized controlled trials and long-term research are needed to confirm these findings and develop more reliable clinical guidelines for its use in children and adolescents with UC. This means that even if the initial findings are promising, additional and better testing is required to ensure that vedolizumab is both effective and safe for young patients with UC. TRIAL REGISTRATION: The PROSPERO registration number for this systematic review is CRD420250651513.