Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain-heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.