Abstract Current management of anesthesia‐associated complications falls short in terms of both efficacy and safety. Nanomaterials with versatile properties and unique nano‐bio interactions hold substantial promise as therapeutics for addressing these complications. This review conducts a thorough examination of the existing nanotherapeutics and highlights the strategies for developing prospective nanomedicines to mitigate anesthetics‐related toxicity. Initially, general, regional, and local anesthesia along with the commonly used anesthetics and related prevalent side effects are introduced. Furthermore, employing nanotechnology to prevent and alleviate the complications of anesthetics is systematically demonstrated from three aspects, that is, developing 1) safe nano‐formulization for anesthetics; 2) nano‐antidotes to sequester overdosed anesthetics and alter their pharmacokinetics; 3) nanomedicines with pharmacodynamic activities to treat anesthetics toxicity. Finally, the prospects and challenges facing the clinical translation of nanotherapeutics for anesthesia‐related complications are discussed. This work provides a comprehensive roadmap for developing effective nanotherapeutics to prevent and mitigate anesthesia‐associated toxicity, which can potentially revolutionize the management of anesthesia complications.