Mycoplasma species represent a broad category of bacteria distinguished by their absence of a solid cell wall, making them unusual among prokaryotes. These organisms are significant pathogens capable of infecting a diverse array of hosts, including people and animals, resulting in varied clinical disorders. The significance of Mycoplasma infections is emphasized by their capacity to induce mixed infections and co-infection with other bacteria and viruses, thereby complicating clinical manifestations, diagnosis, and treatment outcomes. During this review, the considerable relevance of co-infection of Mycoplasma with other mollicutes or with other pathogens is brought to light. Additionally, the report highlights the global risk of Mycoplasma co-infections in recent decades and the synergistic pathogenicity of such co-infections. Networks of Mycoplasma co-infection and diagnostic dilemmas associated with Mycoplasma co-infection were also investigated.