The worldwide prevalence of musculoskeletal disorders is expected to rise due to an accelerating aging population and increasing associated factors. Despite the high rate of disability induction, clinical options for the treatment of musculoskeletal disorders remain limited. Hydrogel microspheres (HMSs), which are colloidal particles with crosslinked polymer networks at the nanometer scale, are characterized by excellent biocompatibility, easy-to-tune structures (e.g., stiffness, porosity, and composition), and high encapsulation efficiency of therapeutic agents (e.g., drugs and cells). At present, multiple techniques are utilized for the fabrication of HMSs and encapsulation of therapeutic agents. The HMSs can be produced and used in different states to match specific utilizations. These desirable properties, along with their injectability, bestow HMSs with mutifunctionalities that can be utilized for a variety of biomedical applications (e.g., delivery of biologics, tissue regeneration, and bio-lubrication), and thus enable them to be promising tools for tackling a variety of clinical diseases. Herein, the focus is the fabrication and application of therapeutic HMSs for i) bone disorders, ii) cartilage and osteochondral disorders, iii) intervertebral disc (IVD) disorders, and iv) neurovascular disorders, with the aim of overviewing the recent progress to summarize key contributions and findings and highlight the limitations and opportunities in this field. This review provides an overview of bio-functional hydrogel microspheres (HMSs) as injectable theranostic biomaterials for a variety of biomedical applications (e.g., delivery of biologics, tissue regeneration, and bio-lubrication), which are anticipated to tackle a variety of musculoskeletal disorders (e.g., bone, joint, IVD, and neurovascular diseases) in the clinic and exhibit considerable potential for clinical translation. image