α-Lipoic acid (ALA) is a naturally occurring compound with diverse biological functions, widely distributed in animal and plant tissues. It has attracted considerable attention due to its versatile therapeutic potential. However, despite these promising prospects, the clinical application of ALA remains limited by its low bioavailability and chemical instability and an incomplete understanding of its multifaceted mechanisms across various diseases. This review provides a comprehensive overview of the biochemical properties of ALA, including its direct free-radical-scavenging activity, regeneration of endogenous antioxidants, chelation of metal ions, and modulation of inflammatory responses. We also highlight the current evidence regarding ALA's therapeutic roles and efficacy in major diseases, such as neurodegenerative disorders, lung diseases, cardiovascular diseases, and diabetes. Furthermore, recent advancements and innovative strategies in ALA-based derivatives and drug-delivery systems are summarized, emphasizing their potential to address complex diseases and the necessity for further translational studies. This review aims to provide a theoretical foundation for the rational design of ALA-based therapies, thereby supporting future clinical applications and the optimization of therapeutic strategies.