Microfluidization (50-150 MPa) and thermal treatment (45-85 °C) were applied to modulate the physicochemical stability, molecular interaction and microstructure of zein-proplyene glycol alginate (PGA)-tea saponin (TS) complex nanoparticles for delivery of curcumin. The size of these complex nanoparticles was decreased from 583.1 to 267.4 nm as the microfluidization pressure was increased from 0 to 100 MPa. In the combined treatment of microfluidization and heating, 100 MPa and 75 °C were the optimum parameters to prepare zein-PGA-TS complex nanoparticles for a better protection of curcumin against various environmental stresses. SEM revealed a synergistic effect of microfluidization and heating on the fabrication of complex nanoparticles with a more uniform size and spherical shape. During in vitro gastrointestinal digestion, the complex nanoparticles showed an excellent gastric stability and a sustained release of curcumin in the small intestinal phase. These findings interpreted the effects of microfluidization and thermal treatment on the functional properties of protein-polysaccharide-surfactant complex nanoparticles that can be utilized to develop food grade nanoparticles with enhanced stability and controllable digestion behaviour.