Abstract: The aim of this study was to investigate the effects of in vitro simulated digestion on the stability and structure of oyster protein hydrolysate zinc nanoparticles (OPH-Zn), and to reveal the dynamic variation rule of OPH-Zn under different degrees of gastrointestinal digestion. Atomic absorption spectrophotometer, UV scanner, infrared spectrometer, fluorescence spectrometer, scanning electron microscope, transmission electron microscope and particle size analyzer were used to determine the zinc content, surface morphology, secondary structure and molecular weight distribution of OPH-Zn in digestive fluid in simulated gastrointestinal digestion process. The results showed that the total zinc content of OPH-Zn was 228.89±2.53 mg/g. During simulated gastric digestion, soluble zinc content in OPH-Zn and ZnSO₄ controls remained stable basically, and there was no significant difference between the two samples (P>0.05). When the digestion was transferred from the stomach to the intestine, the zinc solubility of OPH-Zn and ZnSO₄ decreased by 28.07% and 55.31% (P<0.05), respectively. The soluble zinc content of OPH-Zn was significantly higher than that of ZnSO₄ during the whole intestinal digestion (P<0.05). The spectral analysis showed that OPH-Zn remained relatively stable in simulated gastric juice and intestinal juice, but the coordination between the oxygen and nitrogen atoms of peptide bond and Zn²⁺ was changed during the transition from gastric juice to intestinal juice. The results of electron microscopy showed that the surface microstructure and particle size of OPH-Zn were different with different levels of digestion. The results revealed that the OPH-Zn had a certain stability in simulating gastrointestinal digestion and was a potential zinc supplement with commercial potential. At the same time, the structural changes of OPH-Zn would also provide a certain research basis for the development and follow-up study of peptide-zinc nanoparticles.