Cross-linkers are pivotal to meliorate the attributes of the biopolymers, which are exploited in the biomedical industries, and also those intended as packaging supplies. Genipin (GN) is an efficacious cross-linker. Moreover, being naturally procured, biodegradable and biocompatible makes it an auspicious candidate for the biomedical and food industries. Accordingly, we attempted to provide a comprehensive review on GN as an efficient cross-linker for biopolymers. Initially, we presented the chief botanical sources of GN. The GN extraction strategies, which adopted safe solvents, were then discussed while highlighting their realized yields. The proposed GN structures, its possible modes of action, and the factors affecting its interactions, such as pH, temperature, and GN concentration were also reviewed. Afterward, the GN applications that mainly involved cross-linking biopolymers and biopolymers containing materials were discussed. These included tissue engineering, wound dressings, drug delivery, and packaging applications. GN capability to activate biopolymers, such as chitosan and gelatin, into covalently reactive enzyme immobilizers was also discussed. Moreover, other important GN applications, such as exploiting it as a colorant for foods and textiles and incorporating it in altered biosensors, were discussed.