Intoxication is one of the most common causes of accidental death globally. Although some antidotes capable of neutralizing the toxicity of certain xenobiotics have become well established, the current reality is that clinicians primarily rely on nonspecific extracorporeal techniques to remove toxins. Nano-intervention strategies in which nanoantidotes neutralize toxicity in situ via physical interaction, chemical bonding, or biomimetic clearance have begun to show clinical potential. However, most nanoantidotes remain in the proof-of-concept stage, and the difficulty of constructing clinical relevance models and the unclear pharmacokinetics of nanoantidotes hinder their translation to clinic. This Concept reviews the detoxification mechanisms of polymer nanoantidotes and predicts the opportunities and challenges associated with their clinical application.