Osteopathic manipulative treatment (OMT) is a hands-on therapy aiming to achieve the global homeostasis of the patient. OMT focuses on treating the somatic dysfunctions characterized by tissue modifications, body asymmetry, and range-of-motion restrictions. The benefits related to OMT are thought to be associated with the interconnectedness of the body’s systems and the inherent capacity for self-healing. However, whether OMT can influence brain activity, and, consequently, neurophysiological responses is an open research question. Our research investigates the literature to identify the effects of OMT on brain activity. The main purpose of the research question is: can OMT influence brain activity and consequently neurophysiological responses? A scoping review was conducted, searching the following databases: PubMed, Google Scholar, and OSTEOMED.DR (Osteopathic Medical Digital Repository), Scopus, Web of Science (WoS), and Science Direct. The initial search returned 114 articles, and after removing duplicates, 69 were considered eligible to be included in the final sample. In the end, eight studies (six randomized controlled trials, one pilot study, and one cross-over study) were finally included and analyzed in this review. In conclusion, OMT seems to have a role in influencing functional changes in brain activity in healthy individuals and even more in patients with chronic musculoskeletal pain. However, further RCT studies are needed to confirm these findings. Registration protocol: CRD42024525390.