Genipin (GN) is a natural cross-linker derived from *Genipa americana* and *Gardenia jasminoides* fruits, known for its therapeutic properties and biocompatibility. This review provides a comprehensive overview of GN as an efficient cross-linker for biopolymers, covering its botanical sources, extraction methods, structure, mode of action, and applications. GN extraction is discussed using safe solvents like water, ethanol, natural deep eutectic solvents (NADESs), and milk, with a focus on yield and eco-friendliness. The structure of GN and its interaction mechanisms with primary amine residues are detailed, highlighting the formation of Schiff's base and heterocyclic complexes. The influence of pH, amino acid type, temperature, and GN concentration on GN interactions is explored, emphasizing the role of these factors in cross-linking efficiency and product properties. GN applications in tissue engineering, wound dressings, drug delivery, and packaging are reviewed, along with its use as a colorant in food and textiles and in immobilizing enzymes. The review underscores GN's potential as a safe and effective cross-linker for enhancing the stability and functionality of biopolymers.Genipin (GN) is a natural cross-linker derived from *Genipa americana* and *Gardenia jasminoides* fruits, known for its therapeutic properties and biocompatibility. This review provides a comprehensive overview of GN as an efficient cross-linker for biopolymers, covering its botanical sources, extraction methods, structure, mode of action, and applications. GN extraction is discussed using safe solvents like water, ethanol, natural deep eutectic solvents (NADESs), and milk, with a focus on yield and eco-friendliness. The structure of GN and its interaction mechanisms with primary amine residues are detailed, highlighting the formation of Schiff's base and heterocyclic complexes. The influence of pH, amino acid type, temperature, and GN concentration on GN interactions is explored, emphasizing the role of these factors in cross-linking efficiency and product properties. GN applications in tissue engineering, wound dressings, drug delivery, and packaging are reviewed, along with its use as a colorant in food and textiles and in immobilizing enzymes. The review underscores GN's potential as a safe and effective cross-linker for enhancing the stability and functionality of biopolymers.