Abstract: Molecular pharmaceutics is a discipline that studies the law and mechanism of preparations at the molecular level. It can clarify the forming principle of transdermal drug delivery and the molecular mechanism of drug release and transdermal penetration affected by the molecular interaction among drugs, matrices and organisms. In recent years, molecular pharmaceutics has been applied more and more in transdermal drug delivery. In this paper, the application of molecular pharmaceutics in transdermal drug delivery preparations of traditional Chinese medicine was reviewed, and the molecular interaction of transdermal drug delivery in preparation, drug release and skin penetration, as well as the molecular mechanism of penetration enhancer in traditional Chinese medicine promoting drug penetration into skin was investigated. It provides reference for the application of molecular pharmaceutics in the study of transdermal drug delivery preparations, so as to promote the development and wide application of transdermal drug delivery preparations of traditional Chinese medicine.