Abstract: This paper delves deeply into the historical understanding and evolution of drug toxicity within the materia medica, aiming to provide valuable insights for both theoretical research and clinical application regarding the toxicity of traditional Chinese medicine (TCM). Throughout the development of materia medica studies, the theory of TCM toxicity has been continuously refined and enriched. It has progressively elucidated the core connotations of toxicity—such as dispelling pathogenic factors to support healthy qi, the bias of medicinal properties, and impairing healthy qi and harming life—thereby enriching the understanding of toxic medicinal substances and their degrees of toxicity. Concurrently, the clinical application of toxic drugs—particularly in the context of syndrome differentiation, as well as methods for toxicity prevention, mitigation, and detoxification—has become increasingly sophisticated. This evolution has laid a solid foundation for the theoretical development and safe application of modern toxic TCM. In particular, it holds significant guiding value for toxicity-efficacy transformation based on syndrome differentiation, and the use of highly toxic medicines in treating stubborn and severe diseases.