ObjectiveTo review the research progress of novel cross-linking methods applied in bio-derived materials. MethodsThe literature about the latest progress in the cross-linking methods of bio-derived materials was reviewed and analyzed. ResultsThe novel cross-linking methods of the bio-derived materials can be divided into chemical methods, physical methods, and biological methods, whose available application and cross-linking properties are greatly depended on their mechanisms. So proper methods should be developed to meet the various application requirements of the materials. A series of studies shows the feasibility and availability of the cross-linked bio-derived materials in the repair and reconstruction of the tissue. ConclusionBio-derived materials modified by novel cross-linking methods are proved to obtain excellent biocompatibility and tissue repair ability, better mechanical properties and degradation properties, and so on. Those methods provide researchers more choices to cross-linking materials, which are help to obtain the clinical tissue engineering products.