As consumer demands evolve for health supplements, traditional ginseng products are facing challenges in enhancing their powder characteristics and bioavailability. The objective of this study was to prepare a novel ginseng superfine powder using a high-pressure homogenization (HPH) process. Response surface methodology was employed to determine the effects of HPH parameters (pressure, number of passes, and concentration) on particle size and the dissolution of the saponin components of the superfine powders. The Box-Behnken design of experiments was applied to ascertain the optimal HPH parameters for the smallest particle size and the highest dissolution of the saponin components. For the powders obtained at different parameters, the characterization of tap density, bulk density, flowability, water-holding capacity, appearance, and taste were observed. The optimized experimental conditions for the HPH process were as follows: 15,000 psi (pressure), 3 (number of passes), and 1 kg/L (concentration). The optimized values were 55 μm (particle size) and 83 mg/g (dissolution of the saponin components), respectively. The method offered technical support for the application of the HPH process in the preparation of ginseng powders. The objects of this research could be broadened to include a diverse array of botanical materials, addressing contemporary demands for cost-effectiveness and sustainability within the industry.