With the advancement of perinatal medicine and neonatal surgical techniques, the use of anesthetic agents in neonates and infants has become increasingly widespread. However, the developing nervous system exhibits unique sensitivity to anesthetics, raising significant concerns regarding their safety. Although inhalational anesthetics (such as isoflurane and sevoflurane) and intravenous anesthetics (such as propofol, phenobarbital, and midazolam) are widely applied, animal studies have demonstrated their potential to induce neuronal apoptosis and impair synaptic development, while clinical observations have also suggested associations with neurodevelopmental outcomes. This review summarizes the physiological and pharmacokinetic characteristics of neonates, the neurotoxic mechanisms and clinical safety evidence of commonly used anesthetic agents, with a particular focus on intervention and neuroprotection strategies. Intervention measures include optimization of anesthetic selection, individualized dosing, co-administration of neuroprotective agents, and implementation of precision anesthesia management models. Future research should focus on the development of novel safe anesthetic agents, exploration of epigenetic and neuroprotective mechanisms, and establishment of individualized management models based on multidisciplinary collaboration to ensure the safety and efficacy of anesthesia in neonates and infants.

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