Benign masseter hypertrophy causes swelling at the angulus mandibulae and may be associated with masticatory myofascial pain due to hyperfunction from bruxism. The aim of this research was to use the systematic review process to investigate the true or reliable scientific evidence contained in four major databases pertaining to the efficacy and safety of intra-muscular injections of botulinum toxin A (BTX-A) for the treatment of masticatory myofascial pain and benign masseter hypertrophy associated with bruxism, compared with placebo or other traditional treatments prescribed for bruxism such as occlusal splints, pharmacotherapy, or lifestyle modification. Using the PICO format, a research question was formulated, MeSH terms were derived, and an electronic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane. This sequence was followed by a screening and selection of articles by two independent reviewers according to defined inclusion and exclusion criteria. The selected studies were then evaluated and assessed based on study quality and identification of biases, and the results were summarized and reported. This review highlighted the lack of well-designed, randomized controlled trials to evaluate the efficacy and safety of botulinum toxin A for reducing the size/volume of the masseter muscles and for improving masticatory myofascial pain in patients who present with bruxism. Thus, the results were inconclusive.