The purpose of this review is to elaborate the role of Periplaneta (P.) americana L. in modern and traditional Chinese medicine (TCM) and compare the use of the species in these two forms of medical treatments. From searches on Google Scholar, PubMed, and Web of Science databases, studies were identified involving TCMs with P. americana, which have a history of use over several thousand years, and demonstrate how extracts from this insect play a role in the treatment of diseases through antibacterial, antiviral, antitumor activity, and enhancement of immune function. Extracts from P. americana have not been fully developed for clinical use because the active components have not been completely purified or their molecular mechanisms thoroughly understood. The development of extraction technology in modern Chinese medicine has revealed that many extracts from P. americana are able to play an important role in the control of diseases such as cancer. Drugs such as ‘Kangfuxin Solution’ and ‘Xinmailong Injection’ are now widely used for gastrointestinal ulcers and chronic heart failure, having achieved beneficial curative effects in clinical studies. Based on this, the information from studies of P. americana in TCM and modern medicine should be combined and their respective advantages applied. This review provides an overview of the role of P. americana in modern and TCM and thus contributes to identification of further applications and area requiring drug development.