OBJECTIVE: To review the application of genipin for the modification of natural biomaterials as a crosslinking agent and progress in research. METHODS: Domestic and foreign literature on application of genipin for the modification of natural biomaterials as a crosslinking agent was thoroughly reviewed. Results Genipin is an effective natural crosslinking agent with a very low level of cytotoxicity compared with conventional synthetic crosslinking agents. Tissues fixed with genipin can maintain a high level of stability as well as resistance to enzymatic degradation. CONCLUSION: Genipin is a promising substitute for conventional synthetic crosslinking agents, which has offered an alternative for modification of natural biomaterials for tissue engineering.