Dexmedetomidine is a highly selective α₂ adrenergic receptor agonist, exerting anti-sympathetic, sedative, analgesic and anti-anxiety effects, with minimal impact on respiration. In recent years, dexmedetomidine has been widely used in clinical anesthesia, perioperative treatment, and intensive care. Organ-protection is an important focus of anesthesia and perioperative medicine, with clinical significance in reducing complications and improving short- and long-term outcomes. Increasing clinical evidence and basic research have shown that the application of dexmedetomidine could protect the heart, brain, lung, kidney, liver, gastrointestinal tract and other important organs. The mechanism may be related to dexmedetomidine's effects of anti-inflammation, anti-oxidation, anti-apoptosis, and autophagy regulation. From our perspectives, clinical use should follow the principle of individualization, and the dose should be adjusted in time according to patients' responses, so as to avoid adverse reactions such as hypotension and bradycardia while protecting the organs. Moreover, more strictly designed clinical studies and in-depth mechanistic investigations are needed for the optimal dexmedetomidine therapy and better organ protection during the perioperative course. In order to facilitate better understanding of clinicians, this paper reviews the organ-protective effects and underlying mechanisms of dexmedetomidine.