Purpose: This study assessed the comparative efficacy and safety of tumor necrosis factor alpha (TNF-alpha) inhibitors in treating noninfectious uveitis (NIU). Methods: A comprehensive search was performed in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang Database from January 2010 to March 2024. The outcomes measured included inflammation improvement, visual acuity (VA) improvement, corticosteroid (CS)-sparing effect, central macular thickness (CMT) reduction, and adverse event incidence. Meta-analyses were conducted using RevMan 5.4 and Stata 16 software. Results: A total of 40 studies were included, involving 3,250 patients. TNF-alpha inhibitors showed a 90.4% inflammation improvement rate [95% confidence interval (CI): 0.770-0.987], 35.2% VA improvement (95% CI: 0.152-0.553), 55.3% CS-sparing effect (95% CI: 0.297-0.796), and CMT reduction of 62.37 mu m (95% CI: 45.41-79.32 mu m). Adverse events occurred in 24.0% of patients (95% CI: 0.170-0.310). No significant differences were observed between adalimumab and infliximab in inflammation improvement (P = 0.60) or CMT reduction (P = 0.55), but infliximab had higher adverse event rates (P = 0.0001; relative risk = 1.71, 95% CI: 1.30-2.24). Conclusions: This meta-analysis demonstrates that TNF-alpha inhibitors significantly improve inflammation, VA, and reduce CMT and CS use in NIU. While adalimumab and infliximab exhibit comparable efficacy, infliximab is associated with a higher adverse event rate, highlighting the need for personalized treatment.