Esketamine is a potent and safe dextrorotary form of racemic ketamine. It acts on NMDA receptors and non‑NMDA receptor pathways and can produce good sedative and analgesic effects. Esketamine has the advantages of rapid metabolism and few side effects so it is widely used in the perioperative period. This review focuses on the mechanism of action of esketamine, its impact on perioperative physiological functions, and the progress of its application in de‑opioid anesthesia, multimodal analgesia, antidepressant and sleep improvement. It provides a reference for more reasonable and safe clinical application of esketamine. Esketamine may help facilitate postoperative recovery and improve patients' quality of life.