The recent progress in various biomaterials with unique physiological and pharmacological properties has expedited the development of translational medicines for the diagnosis, prognosis, and therapy of intractable diseases. Hyaluronic acid (HA) is one of such biomaterials that has attracted great attention due to its unique characteristics for biomedical applications. In this Perspective, we provide an overview of HA-based medicines in a variety of forms such as chemical and biological conjugates, nanoparticles, nanoparticle hybrid systems, hydrogels, and-nanogels. We highlight the current-state-of-the-art strategies to design and optimize innovative HA-based medicines for their clinical translations. Finally, we discuss the challenges for technical hurdles and the future directions to expand the feasibility of HA-based translational medicines.