Natural polymers have attracted increasing attention for biomedical applications owing to their biocompatibility. Casein possesses several interesting properties that make it a good candidate for biomedical materials. In this context, a novel casein-based nanocomposite was created by adding organized montmorillonite (OMMT) as a reinforcing material and ethylene glycol diglycidyl ether (EGDE) as a cross-linking agent. Fourier transform infrared spectroscopy indicated that EGDE had reacted with casein to form a network structure. X-ray diffraction and transmission electron microscopy showed a transformation of the OMMT structure from exfoliated to intercalated with an increase in the amount of OMMT. Scanning electron microscopy revealed that the nanocomposite with low OMMT content was characterized as high porosity. The addition of OMMT and EGDE improved the physical properties of the casein composites, resulting in a lower swelling ratio, higher thermal stability, lower biodegradation rate, and stronger mechanical properties compared with neat casein. A cell counting kit-8 assay demonstrated that the prepared nanocomposite films are biocompatible. These observations suggest that the casein nanocomposite is a promising material for biomedical applications.