Infectious diseases are a leading cause of mortality worldwide, with viruses and bacteria in particular having enormous impacts on global healthcare. One major challenge in combatting such diseases is a lack of effective drugs or specific treatments. In addition, drug resistance to currently available therapeutics and adverse effects caused by long-term overuse are both serious public health issues. A promising treatment strategy is to employ cell-membrane mimics as decoys to trap and to detain the pathogens. In this Perspective, we briefly review the infection mechanisms adopted by different pathogens at the cellular membrane interface and highlight the applications of cell-membrane-mimicking nanodecoys for systemic protection against infectious diseases. We also discuss the implication of nanodecoy-pathogen complexes in the development of vaccines. We anticipate this Perspective will provide new insights on design and development of advanced materials against emerging infectious diseases.