Objective An evidence-based review on the safety and efficacy of botulinum toxin type-A (BoNTA) in orofacial conditions, focusing on the therapeutic applications and role of BoNTA as an adjuvant treatment.Data source and selection Data was collected using PubMed (Medline), Cochrane Library of Systematic Reviews and Cochrane Central Register of Controlled Trials electronic databases. Having satisfied the search parameters, 32 studies for therapeutic applications and 26 for BoNTA as an adjunctive treatment were included. The quality of relevant studies was assessed using the Best Evidence Topics (BETs) Critical Appraisal Tool.Data extraction The highest level of evidence (LOE) behind BoNTA safety and efficacy was for wound healing and scar management in the orofacial surgery context, where BoNTA was presented as an adjunctive modality. Level-I evidence was controversial for temporomandibular disorders and bruxism. However, it showed promising results for painful temporomandibular disorders of myogenic origin refractory to conservative therapies, and to decrease muscle contraction intensity in sleeping bruxism. There was only one level-II study for persistent recurrent aphthous stomatitis. Data showed limited level-III evidence for orofacial pain conditions (temporomandibular joint recurrent dislocation and pain, burning mouth syndrome or atypical odontalgia), oral cancer complications, or as an adjuvant to maxillofacial and orthognathic surgeries. Benefits of BoNTA in prosthodontics had weak level-IV evidence. No evidence was found among the periodontology field.Conclusion There is growing evidence to support the safety and efficacy of BoNTA in the investigated orofacial pathological conditions, with high levels of satisfaction from the patient and clinician perspective. However, there are some inconsistencies and limited high-quality evidence available. Well-designed controlled clinical trials are necessary to evaluate long-term safety, efficacy and cost-effectiveness before BoNTA is widely adopted with irrefutable evidence-based clinical guidelines.