Aim: To systematically review the efficacy of Botulinum Toxin (BTX) compared to conservative treatment modalities or placebo in the management of Myofascial Pain Dysfunction Syndrome (MPDS) in adults. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed across electronic databases (PubMed, Google Scholar, Science Direct, and Cochrane CENTRAL) and grey literature sources to identify studies evaluating the effect of intramuscular BTX injection for MPDS. Eligible studies included randomized controlled trials (RCTs) involving adult patients (≥18 years) with a clinical diagnosis of MPDS. The interventions consisted of BTX injections into the masticatory muscles, while comparators included other conservative therapies or placebo. The primary outcome was pain reduction (measured via Visual Analogue Scale), and secondary outcomes included changes in maximal mouth opening and reported adverse effects. Risk of bias was assessed independently by three reviewers using the Cochrane Risk of Bias tool. A random-effects model was applied for meta-analysis, with standardized mean difference (SMD) as the summary statistic (p<0.05). Results: Thirteen studies met the inclusion criteria and were included in the qualitative synthesis. The risk of bias was low to moderate across the included studies. The pooled results favored the BTX group over conservative treatments or placebo in terms of pain reduction and improvement in mouth opening. Conclusion: Botulinum toxin appears to be an effective adjunct or alternative to conservative treatments for the management of MPDS, offering superior pain relief and functional improvement. However, due to heterogeneity in study design, dosage, and follow-up duration, further well-designed randomized trials with standardized protocols and long-term outcome assessment are necessary to establish definitive clinical recommendations. Keywords: Botulinum Toxin (BTX), Myofascial Pain Dysfunction Syndrome (MPDS), temporomandibular disorders (TMD)