Sepsis-associated encephalopathy (SAE) is a severe central nervous system complication that is secondary to sepsis and is characterized by a poor prognosis, high mortality, and multiple systemic manifestations. Although the specific etiology remains incompletely understood, SAE typically presents with varying degrees of neurological dysfunction. The complex mechanisms underlying SAE significantly influence patient outcomes. Recent studies have emphasized the roles of blood-brain barrier (BBB) disruption, microglial activation, mitochondrial dysfunction, apoptosis, inflammatory responses, and oxidative stress in the development and progression of SAE. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist initially employed as an anesthetic adjunct, has attracted increasing attention for its therapeutic potential in SAE. Its notable pharmacological properties include anti-inflammatory activity, modulation of microglial responses, regulation of immune function, stabilization of mitochondrial activity, inhibition of apoptosis, and maintenance of hemodynamic stability in patients with sepsis. In addition, dexmedetomidine supports gastrointestinal homeostasis and offers multiorgan protection. This review consolidates current findings regarding the protective mechanisms of dexmedetomidine in sepsis-induced brain injury and provides insight into its potential clinical applications in the management of SAE.