Abstract: To investigate changes in the physicochemical properties of nano delivery systems that were fabricated by native biomacromolecules during digestion, curcumin and zein were separately used as the core and shell materials in this study, and curcumin-loaded zein nanoparticles (CZNPs) were prepared by the way of inverse solvent precipitation. Firstly, the physicochemical properties of CZNPs were characterized by various spectroscopy and electron microscopy methods. Then, the digestive properties of CZNPs in an in vitro simulated digestion model were investigated. Results showed that the encapsulation efficiency of Cur (99%±1%) was the largest when the mass ratio of Cur and zein was 1:40. Moreover, the obtained CZNPs were spherical nanoparticles with an average particle size of 118.6±0.7 nm and zeta potential of 19.9±3.79 mV. Slight adhesion between CZNPs was also noticed. During in vitro simulated gastric digestion, with the increase of digestive time, significant aggregation occurred and the average particle size of CZNPs increased to 8000 nm. Meanwhile, part of zein degraded into amino acids and Cur was released slightly. During the subsequent simulated intestinal digestion, the aggregation of CZNPs reduced with time. However, zein kept stable without continue degradation and the release of Cur didn’t change significantly. Therefore, zein nanoparticles may be an effective oral delivery system with possible applications in the development of functional foods and orally administered drugs.