Acute central nervous system (CNS) injuries are common causes of human disabilities and deaths. Valproic acid (VPA), as a histone deacetylase inhibitor, is mainly used for the treatment of seizure, bipolar affective disorder, neuropathic pain, and migraine in clinical practice. Recent studies have shown that VPA has the features of anti-apoptosis, anti-inflammation, anti-oxidative stress, and neurotrophy and can exert a neuroprotective effect in several models of acute CNS injuries, such as cerebral vascular accident, traumatic brain injury, and spinal cord injury. This article reviews the neuroprotective and repair features of VPA in acute CNS injuries and explores the underlying mechanisms and related factors.