Abstract: Skimmed milk powders were widely used, but they suffer from poor solubility, difficulty in brewing and allergic reactions. Dynamic ultra-high pressure could change the structure and improve the physicochemical properties of many proteins and liquid foods. In this study, skim milk powder was selected as the research subject, and was treated with varying pressures (50, 100, 150, 200, 250 MPa) of dynamic ultra-high pressure. Techniques such as electrophoresis, spectroscopy, and enzyme-linked immunosorbent assay were employed to analyze the changes of structure and physicochemical properties. The results showed that, the particle size, turbidity and free sulfhydryl of skimmed milk powder gradually decreased with the increase of dynamic ultrahigh-pressure treatment pressure. The intrinsic fluorescence and surface hydrophobicity of the skimmed milk powder showed an increasing trend, and reached the maximum at 250 MPa. The solubility, foaming and emulsification properties improved, reaching their peak at 250 MPa. Additionally, the degree of caking was reduced. The IgE-binding capacity initially increased, then decreased, reaching its lowest point at 250 MPa. Therefore, dynamic ultra-high pressure could alter the structure of skim milk powder, and improve the physicochemical properties, with greater effects observed at higher pressures. This study provides crucial theoretical insights into the application of dynamic ultra-high pressure in food processing and the production of nutritious and healthy dairy products.