Abstract: Chondroitin sulfate proteoglycans (CSPGs), which are glycoconjugates covalently linked by chondroitin sulfate (CS) and core protein, exist on the cell surface and connective tissues. With the rapid development of the field of CSPGs in recent years, CSPGs are not only considered as structural components of complex matrix such as cartilage, intervertebral discs, brain, and cornea, they can also interact with various bioactive molecules and participate in physiopathological processes such as angiogenesis, inflammatory responses, tumorigenesis, and neurodevelopment. Studies have shown that the type, molecular weight, and sulfation degree of CS glycans would affect the biological function of CSPGs. In addition, CSPGs have been considered as therapeutic targets and potential diagnostic biomarkers of diseases such as cancer and central nervous system injury. According to the location of CSPGs in cells, this article reviews the recent advances in the structure and function of typical CSPGs as well as their biological significance as targets for disease diagnosis and treatment, aiming to provide reference for promoting the application of CSPGs in disease therapy.