Traumatic brain injury (TBI) can simply be defined as a violent external injury to the head causing brain dysfunction. The primary injury occurs immediately on impact whereas the secondary injury begins minutes to months after impact. TBI affects a vast majority of population worldwide yet, there isn't any therapeutic intervention available. Sirtuins (SIRTs) are important regulator proteins found in humans. In several neurodegenerative diseases, SIRTs have proven its neuroprotective actions. Owing to the pathophysiological similarities in these diseases and TBI, SIRTs may serve as a potential target for therapeutic intervention in TBI. This review aims to describe the relevance of SIRTs as a potential pharmacological target in TBI. Also, the experimental animal model of TBI explored to understand the role of SIRTs in TBI have been discussed.