Esketamine is a novel intravenous anesthetic drug, which has been widely used in clinical practice due to its unique advantages over ketamine. In recent years, an increasing number of studies have begun to focus on the organ protection effects of esketamine. The mechanisms involve regulating inflammatory responses, reducing cell death, and counteracting oxidative stress. This article reviews the research progress on the protective effects of esketamine on the heart, brain, lungs, liver, intestine, and skeletal muscles, aiming to provide references for the clinical application of esketamine.