〔Abstract〕 Respiratory diseases represent prevalent conditions that pose a significant threat to public health. The pathogenesis of these diseases is complex involving a variety of cells and cytokines. Cell culture technology serves as a fundamental tool for investigating pathological mechanisms and drug efficacy. However, traditional monolayer cell culture fail to mimic the intricate cell-cell interactions, limiting its applicability. In contrast, cell co-culture offers a more physiologically relevant approach by closely mimicking the multicellular microenvironment. This advancement provides a robust model for elucidating pathological pathways and evaluating pharmacological interventions in respiratory diseases. In this review, the applications of cell co-culture technologies in common respiratory diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer, asthma, and pneumonia are summarized, in order to propose strategies for the prevention and treatment of these diseases.