Abstract: Collagen (COL) is a green and renewable organic natural polymer material with excellent biocompatibility, biodegradability and low antigenicity. A series of novel collagen-based nanocomposites combining excellent properties of two components could be developed by introducing inorganic nanomaterials with unique functional characteristics into collagen matrix. However, the interface interaction characteristics between inorganic nanomaterials and organic COL have a significant effect on the properties of the corresponding nanocomposites. Therefore, it is necessary to investigate the interface interaction between nanomaterials and COL. This paper systematically reviewed the main research status of the effect of unmodified/modified nanomaterials on the properties of COL-based nanocomposite, and summarized the progress of the interface research between nanomaterials and COL through methods of modern instrumental analysis and molecular dynamics simulation. Moreover, the advantages and disadvantages of the two methods were compared. Finally, the possible future research trend of the interface interaction between nanomaterials and COL matrix was prospected. It is pointed out that the introduction of nanomaterials into the COL matrix to prepare environmentally friendly, multi-functional, high-performance, and widely used COL-based nanocomposites, and the combination of modern instrument analysis methods and computer simulation methods to conduct interface research will be the main research directions in the future.