In this study, genipin served as crosslinker to combine sodium caseinate (SC) and chitosan oligosaccharide (COS), aiming to improve the physicochemical properties and encapsulation efficiency of SC in delivering hydrophobic nutritional factors. The genipin crosslinked complex of SC and COS (GSCC) was characterized by circular dichroism spectrum and infrared spectrum analyses. Nanoparticles produced from GSCC (GSCCNP) exhibited a superior hydrophilicity compared to those derived from SC (SCNP). GSCCNP significantly augmented the encapsulation efficacy and photostability of β-carotene. β-Carotene encapsulated within GSCCNP (βC-GSCCNP) exhibited remarkable in vitro sustained release characteristics and heightened bioavailability. In addition, βC-GSCCNP showed significant in vitro anti-inflammatory activity. These findings indicated that genipin crosslinking COS-modified SC could construct a nano-delivery system to enhance the stability and bioavailability of insoluble nutritional factors, thereby presenting promising applications for hydrophobic nutrients in the development of functional foods and beverages.