AIM：To comprehensively evaluate the efficacy and safety of rituximab (RTX), tocilizumab (TCZ), and teprotumumab (TMB) in the treatment of thyroid-associated ophthalmopathy (TAO). METHODS: A systematic search was conducted in PubMed, Embase and Cochrane Library databases for systematic reviews/meta-analyses on TAO treatment, with the search time limited to January 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, Assessment of Multiple Systematic Reviews (AMSTAR) 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) were used to assess the reporting quality, methodological quality, and evidence quality of the included studies. RESULTS: The current systematic reviews on the three monoclonal antibodies in TAO treatment exhibited deficiencies in reporting quality, methodological quality, and evidence quality. Direct comparative evidence between the three monoclonal antibodies is still lacking. Based on indirect comparative evidence, TCZ appears to be the most promising treatment option, followed by TMB and RTX. In terms of efficacy, TCZ and TMB significantly reduced the Clinical Activity Score (CAS), proptosis, and improved quality of life. TCZ also significantly reduced the incidence of diplopia. RTX significantly reduced disease response, while RTX and TCZ both significantly improved disease inactivation rates. RTX showed no significant difference in diplopia, lid fissure changes, NOSPECS score and quality of life. The conclusions regarding safety are inconsistent, with TCZ and TMB potentially increasing the incidence of adverse events, while RTX showed no significant difference in safety compared to glucocorticoids or placebo.CONCLUSION: This study provides evidence-based insights for the selection of three monoclonal antibodies in the treatment of TAO. While TCZ may have advantages in efficacy, considering the limitations of existing evidence, more high-quality studies are needed to further verify and compare the efficacy and safety of different monoclonal antibodies in TAO treatment.