Abstract: This study synthesized hawthorn polyphenol microparticles (HPM) based on the polyelectrolyte self-assembly technology. Plackett-burman combined with Box-Behnken design was used to study the factors affecting the preparation of HPM in response to the encapsulation efficiency and drug loading of hawthorn polyphenols. The Plackett-Burman design was used to screen for factors that significantly affect the outcomes, such as preparation time, sulfuric acid concentration, and the ratio of encapsulating materials, which were optimized through Box-Behnken response surface methodology. The morphology of HPM was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and their gastrointestinal release kinetics were assessed using simulated gastric and intestinal fluids. The results indicated that the preparation time, sulfuric acid concentration, and the ratio of encapsulating materials significantly effect the fabrication of HPM. An encapsulation efficiency of 96.27%±1.37% was achieved with a preparation time of 3 h, a sulfuric acid concentration of 0.0254%, and a 4:1 ratio of chitosan to sodium alginate. Morphological analysis of HPM revealed irregularly shaped, well-dispersed spherical particles. The release rate of HPM in simulated intestinal fluid was higher than in gastric fluid, with the release kinetics corresponding to zero-order in gastric fluid and first-order in intestinal fluid. In summary, this study successfully produced HPM with a high encapsulation efficiency, substantial drug loading, and good dispersion. The HPM formulated could reduce the degradation of hawthorn polyphenols in the gastrointestinal tract, offering a novel approach for incorporating hawthorn polyphenols into food products.