Masticatory system disorders—including temporomandibular disorders (TMDs), sleep bruxism, and masseter hypertrophy—have multifactorial origins and significantly affect function and quality of life. Botulinum Neurotoxin Type A (BoNT-A) is increasingly used therapeutically due to its ability to reduce muscle hyperactivity and influence pain pathways. Nonetheless, uncertainties persist regarding long-term outcomes, neuromuscular adaptations, and functional compromises. A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2015 and 2025. Eligible studies included human research evaluating BoNT-A injections for masticatory disorders, including randomized controlled trials, controlled clinical studies, and cohort studies. Outcomes of interest included pain reduction, muscle activity, functional performance, adverse effects, and compensatory mechanisms. Risk of bias was assessed using ROBINS-I and RoB-2 tools. Fourteen studies met the inclusion criteria. BoNT-A consistently reduced pain levels, decreased muscle hyperactivity (confirmed by EMG), and reduced masseter and temporalis muscle thickness. Improvements in mandibular mobility and psychosocial outcomes were also observed. However, compensatory increases in activity or hypertrophy in untreated muscles, reduced bite force, and variability in treatment duration were reported. Interventions involving deeper muscles, such as the lateral pterygoid, showed a higher frequency of adverse effects, including dysphagia. Most studies presented a moderate risk of bias due to methodological limitations. BoNT-A is an effective option for managing masticatory disorders, providing meaningful pain relief and functional improvement. However, its clinical use should consider potential adaptive neuromuscular changes and functional trade-offs. These findings support the need for individualized treatment strategies and multidisciplinary approaches. Future studies should focus on long-term outcomes, biomechanical analysis, standardized protocols, and identifying patient profiles most likely to benefit.
Dipalma et al. (Fri,) studied this question.