Introduction <p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with 80% of ALS patients experiencing bulbar weakness at some stage of the disease. ALS patients with bulbar weakness often suffer from troublesome sialorrhea. Botulinum toxin injection, as a neuromuscular blocker, has been widely used in the treatment of sialorrhea. This paper evaluates the safety and efficacy of botulinum toxin injections for the treatment of sialorrhea in ALS patients through a systematic review and meta-analysis.</p> Methods <p>A systematic review and meta-analysis was conducted by searching eight databases, including PubMed, EMBASE, and CNKI, up to April 13, 2025. Eligible randomized controlled trials and quasi-experimental studies were analyzed using Review Manager 5.4 and Stata software.</p> Results <p>Thirteen studies (2 RCTs, 11 quasi-experimental studies) with 130 ALS patients were included. Botulinum toxin significantly reduced sialorrhea and improved quality of life (Z = 10.98, <i>p</i> &lt; 0.00001; RD = 0.82, 95% CI: 0.67–0.97). The treatment effect was independent of toxin type (<i>p</i> = 0.48), injection site (<i>p</i> = 0.17), and ultrasound guidance use (<i>p</i> = 0.44).</p> Conclusion <p>Botulinum toxin appears to be a safe and effective option for managing sialorrhea in ALS patients, regardless of injection technique. However, given that most included studies were observational, further validation through high-quality RCTs is warranted.</p> Trial registration <p>This meta-analysis has been registered with Prospero, and the registration number is CRD420251029441. The registration period is April 9, 2025.</p>