Dexmedetomidine is a promising alternative sedative agent for moderate-severe Traumatic brain injury (TBI) patients. Although the data are limited, the posited benefits of dexmedetomidine in this population are a reduction in secondary brain injury compared with current standard sedative regimens. In this scoping review, we critically appraised the literature to examine the effects of dexmedetomidine in patients with moderate-severe TBI to examine the safety, efficacy, and cerebral and systemic physiological outcomes within this population. We sought to identify gaps in the literature and generate directions for future research. Two researchers and a librarian queried PubMed, Embase, Scopus, and APA PsycINFO databases. Of 920 studies imported for screening, 11 were identified for inclusion in the review. The primary outcomes in the included studied were cerebral physiology, systemic hemodynamics, sedation levels and delirium, and the presence of paroxysmal sympathetic hyperactivity. Dexmedetomidine dosing ranged from 0.2 to 1 ug/kg/h, with 3 studies using initial boluses of 0.8 to 1.0 ug/kg over 10 minutes. Dexmedetomidine used independently or as an adjunct seems to exhibit a similar hemodynamic safety profile compared with standard sedation regimens, albeit with transient episodes of bradycardia and hypotension, decrease episodes of agitation and may serve to alleviate symptoms of sympathetic hyperactivity. This scoping review suggests that dexmedetomidine is a safe and efficacious sedation strategy in patients with TBI. Given its rapid onset of action and anxiolytic properties, dexmedetomidine may serve as a feasible sedative for TBI patients.