Collagen is the most abundant protein in the human body, with excellent physicochemical properties and biological functions, thus being widely used in fields such as medical cosmetology and injury repair. Mesotherapy is a minimally invasive technology that directly delivers therapeutic materials to the subcutaneous layer, attracting much attention due to its advantages of convenience, safety, rapid effect and mild pain. This paper introduces the basic characteristics and functions of collagen, focuses on its applications in mesotherapy, including aesthetic plastic surgery, musculoskeletal diseases, urogenital system, etc., and elaborates on its mechanism, clinical effects and related adverse reactions. Collagen combined with mesotherapy shows great potential in multiple clinical fields, but there are also some limitations, such as adverse reactions, high requirements for storage conditions, and the need for repeated injections. In the future, with the continuous deepening of research on the mechanism and pathophysiology of collagen, combined with the development of advanced biotechnology, the application of collagen in mesotherapy is expected to be further expanded and optimized, providing more scientific basis and new ideas for clinical treatment.