The application of nanoparticles in the diagnosis and treatment of diseases has undergone different developmental stages, but phagocytosis and nonspecific distribution have been the main factors restricting the transformation of nanobased drugs into clinical practice. In the past decade, the design of membrane-coated nanopartides has gained increasing attention. It is hoped that the combination of the cell membrane's natural biological properties and the functional integration of synthetic nanopartide systems can compensate for the shortage of traditional nanopartides. The membrane coating gives the nanopartides unique biological functions such as immune evasion and targeting capability. However, when the encapsulation of monotypic membranes does not meet the diverse demands of biomedicine, the combination of different cell membranes may offer more possibilities. In this review, the composition, preparation, and advantages of biomimetic nanopartides coated with hybrid cell membranes are summarized, and the applications of hybrid membrane-coated biomimetic nanoparticles (HM@BNPs) in drug delivery, phototherapy, liquid biopsy, tumor vaccines, immune therapy, and detoxification are reviewed. Finally, the current challenges and opportunities with regard to HM@BNPs are discussed.