Abstract: This study aimed to treat grape pomace-derived soluble dietary fiber (SDF) using two modification methods, optimize the modification parameters, compare the physicochemical properties of SDF before and after modification, and investigate its hypolipidemic effects in hyperlipidemic mice, thereby providing a theoretical basis for in-depth research on grape pomace SDF and food development. Using grape pomace SDF as the raw material, it was subjected to modification by microwave-acid (M-A) and cellulase-ultrasound wave (C-UW) methods. Based on single-factor experiments, response surface methodology was employed to optimize the experimental conditions and determine the optimal parameter combinations for modification. The physicochemical properties (including functional characteristics, cholesterol adsorption capacity, and cation exchange capacity) of unmodified SDF and the two modified SDF were compared. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses were also conducted. Additionally, a hyperlipidemic mouse model was established to explore the hypolipidemic effects of SDF before and after modification. Through the measurement and analysis of mouse body weight, four lipid profile indicators, serum ALT and AST activities, liver indices, and histological staining of liver sections, the results demonstrated that: For the M-A-modified SDF, the optimal parameters were as follows:solid-to-liquid ratio 1:24.97, microwave power 220.56 W, and microwave time 60.24 s, achieving an SDF yield of 22.17%. For validation, the process parameters were slightly adjusted to citric acid mass fraction 6%, solid-to-liquid ratio 1:25, and microwave power 240 W, resulting in an average SDF yield of 21.74%, with only a minor deviation of 0.41% from the theoretical yield. For the C-UW-modified SDF, the optimal parameters were: cellulase addition 0.38%, enzymatic hydrolysis temperature 54.04℃, and enzymatic hydrolysis time 28.61 min, resulting in an SDF yield of 28.8%. For validation, the process parameters were slightly adjusted to cellulase addition 0.4%, enzymatic hydrolysis temperature 55 ℃, and enzymatic hydrolysis time 30 min, resulting in an average SDF yield of 28.29%, with only a minor deviation of 0.51% from the theoretical yield. In terms of physicochemical properties, C-UW-modified SDF exhibited significant superiority over unmodified SDF and M-A-modified SDF. SEM results showed that C-UW-modified SDF formed a denser, rod-like structure, while FTIR analysis indicated that the main components and overall chemical structure of the three SDFs remained relatively stable without significant changes. These findings confirmed that C-UW-modified SDF demonstrated better modification effects compared to unmodified SDF and M-A-modified SDF. In the mouse experiments, compared to the model group, C-UW SDF significantly reduced TC, TG, and LDL-C, while significantly increasing HDL-C. Compared to other treatment groups (unmodified SDF, M-A SDF), C-UW SDF showed more pronounced effects in improving the four lipid profile indicators, particularly in reducing LDL-C and increasing HDL-C. Additionally, C-UW SDF exhibited a reducing effect on serum ALT and AST activities, an inhibitory effect on weight gain, and alleviated liver damage, protecting the integrity of hepatocytes. These results confirmed that C-UW SDF was more effective in reducing blood lipid levels in hyperlipidemic mice, laying a foundation for subsequent research on grape pomace SDF and food development.