Lipoic acid (LA), an endogenous small molecule in organisms, has been extensively used for the highly efficient clinical treatment of malignant diseases, which include diabetes, Alzheimer's disease, and cancer over the past seven decades. Tremendous progresses have been made on the use of LA in nanomedicine for the development of various biomaterials because of its unique biological properties and highly adaptable structure since the first discovery. However, there are few reviews thus far, to our knowledge, summarizing this hot subject of research of LA and its derived biomaterials. For this purpose, we present herein the first comprehensive summary on the design and development of LA and its derived materials for biomedical applications. This review first discusses the therapeutic use of LA followed by the description of synthesis and preclinical study of LA-derived-small molecules. The applications of various LA and poly (lipoic acid) (PLA)-derived-biomaterials are next summarized in detail with an emphasis on the use of LA for the design of biomaterials and the diverse properties. This review describes the development of LA from a clinical therapeutic agent to a building unit of various biomaterials field, which will promote the further discovery of new therapeutic uses of LA as therapeutic agents and facile development of LA-based derivates with greater performance for biomedical applications.