Dry eye disease (DED) is a complex condition characterized by tear film instability, inflammation, and neurosensory abnormalities. The efficacy of Botulinum toxin A (BTX-A) in treating DED is unknown. A systematic search was conducted across PubMed, the Cochrane Library, Scopus, Web of Science, and Embase databases for studies published until December 2024. Inclusion criteria encompassed randomized controlled trials (RCTs) and non-RCTs examining BTX-A's effects on DED, with TBUT, Schirmer test scores, tear meniscus height (TMH), and OSDI as primary outcomes. Data were synthesized using fixed and random-effects models, accounting for heterogeneity. Fourteen studies (total n = 634 patients) were included. This meta-analysis evaluates the effectiveness of BTX-A in improving outcomes for DED. In 10 studies with 513 participants, BTX-A significantly improved TBUT by 1.79 s (95% CI: 1.48 to 2.10, p <
0.00002), Schirmer test scores by 3.72 mm (95% CI: 3.50 to 3.95, p <
0.00002), and OSDI scores by -7.51 (95% CI: -10.76 to -4.26, p <
0.00002). TMH increased by 0.10 mm (95% CI: 0.08 to 0.11, p <
0.00002). This meta-analysis demonstrates that BTX-A effectively improves clinical outcomes in DED. Post-treatment, TBUT increased by 1.79 s, Schirmer test scores improved by 3.72 mm, OSDI scores decreased by -7.51 points, and TMH increased by 0.10 mm, reflecting enhanced tear stability, production, and symptom relief. These findings support the use of BTX-A in clinical practice as a promising treatment for DED.