General anesthetics may exert potential neurotoxic effects on the developing brain. Histone deacetylase inhibitors (HDACIs) can restore or increase the level of histone acetylation, remodel chromatin structure, and regulate gene transcription and expression. A large number of basic studies have found that HDACIs display a wide range of neuroprotective effects on neurotoxicity and cognitive dysfunction caused by various general anesthetics such as sevoflurane, isoflurane, and propofol. HDACIs are a class of promising therapeutics with potential as neuroprotective agents. This review summarized basic research shreds of evidence of the protective role of HDACIs against anesthesia‑induced developmental neurotoxicity, as well as possible mechanisms including regulating cyclic adenosine monophosphate response element‑binding protein (CREB) transcription factor activity, promoting brain‑derived neurotrophic factor expression, reducing glutamate excitotoxicity, promoting synaptic plasticity‑related protein expression, and correcting abnormal neural electrical activity. This review provides a theoretical basis for the clinically reasonable use of HDACIs as neuroprotective agents against anesthesia neurotoxicity.