This study highlights the efficacy of microfluidic technology in creating curcumin (Cur) loaded zein + shellac (Z + S) hybrid nanoparticles (NPs), presenting a promising avenue for enhancing Cur's availability in the food industry, especially in beverages, and positioning it as a potent antioxidant strategy for applications such as the treatment of enteritis. The study revealed that an increase in the proportion of shellac led to a gradual increase in the particle size of Z + S NPs, while the polydispersity index (PDI) initially decreasing and then increasing. When Cur is encapsulated, an increase in the proportion of shellac resulted in a gradual decrease in particle size and PDI, accompanied by an increase in encapsulation efficiency (EE). When the ratio of zein and shellac remained constant, elevating the Cur concentration led to a gradual decrease in EE and a gradual increase in drug loading. The consistently low Zeta potential (below -20 mV) confirmed the colloidal stability of the NPs, making them suitable for prolonged storage. The NPs exhibited excellent biocompatibility with normal cells and demonstrated effective free radical scavenging capabilities. Mixing of shellac and zein regulated the release profile of Cur from the NPs, mapping the food fate in human body, enhancing the treatment efficacy of ulcerative colitis. In vivo experiment demonstrated that the NPs are able to effectively relieve the dextran sulphate sodium induced enteritis, providing a promising approach for the treatment of ulcerative colitis.