The high rates of morbidity, mortality, and disability associated with traumatic brain injury constitute a significant public health burden, highlighting the need for novel therapeutic approaches. The Sirtuin family are crucial regulators of energy homeostasis, with the sirtuin 1 demonstrating a neuroprotective role in various neurological diseases. This paper elucidates the mechanisms underlying the neuroprotective effects of the Sirtuin 1 in the context of traumatic brain injury. Additionally, it reviews drug studies aimed at targeting the Sirtuin 1 for the treatment of traumatic brain injury.