Osteoarthritis (OA) is a degenerative disease caused by a variety of factors with joint pain as the main symptom, including fibrosis, chapping, ulcers, and loss of cartilage. Traditional treatment can only delay the progression of OA, and classical delivery system have many side effects. In recent years, microspheres have shown great application prospects in the field of OA treatment. Microspheres can support cells, reproduce the natural tissue microenvironment in vitro and in vivo, and are an efficient delivery system for the release of drugs or biological agents, which can promote cell proliferation, migration, and differentiation. Thus, they have been widely used in cartilage repair and regeneration. In this review, preparation processes, basic materials, and functional characteristics of various microspheres commonly used in OA treatment are systematically reviewed. Then it is introduced surface modification strategies that can improve the biological properties of microspheres and discussed a series of applications of microsphere functionalized scaffolds in OA treatment. Finally, based on bibliometrics research, the research development, future potential, and possible research hotspots of microspheres in the field of OA therapy is systematically and dynamically evaluated. The comprehensive and systematic review will bring new understanding to the field of microsphere treatment of OA.