Abstract: Bioelectronic interventions, specifically trigeminal nerve stimulation (TNS), have attracted considerable attention in conditions where cortical spreading depolarizations (CSDs) accompanied by compromised cerebral perfusion may exacerbate neurological damage. While pharmacological interventions have demonstrated initial potential in addressing CSDs, a standardized treatment approach has not yet been established. The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs, particularly emphasizing TNS, and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.