In the cosmetics industry, it is important to develop new materials for functional cosmetics such as whitening, wrinkles, anti-oxidation, and anti-aging, as well as technology to increase absorption when applied to the skin. Therefore, in this study, we tried to optimize the nanoemulsion formulation by utilizing response surface methodology (RSM), an experimental design method. A nanoemulsion was prepared by a high-pressure emulsification method using Glabridin as an active ingredient, and finally, the optimized skin absorption rate of the nanoemulsion was evaluated. Nanoemulsions were prepared by varying the surfactant content, cholesterol content, oil content, polyol content, high-pressure homogenization pressure, and cycling number of high-pressure homogenization as RSM factors. Among them, surfactant content, oil content, high-pressure homogenization pressure, and cycling number of high-pressure homogenization, which are factors that have the greatest influence on particle size, were used as independent variables, and particle size and skin absorption rate of nanoemulsion were used as response variables. A total of 29 experiments were conducted at random, including 5 repetitions of the center point, and the particle size and skin absorption of the prepared nanoemulsion were measured. Based on the results, the formulation with the minimum particle size and maximum skin absorption was optimized, and the surfactant content of 5.0 wt%, oil content of 2.0 wt%, high-pressure homogenization pressure of 1,000 bar, and the cycling number of high-pressure homogenization of 4 pass were derived as the optimal conditions. As the physical properties of the nanoemulsion prepared under optimal conditions, the particle size was 111.6 ± 0.2 nm, the PDI was 0.247 ± 0.014, and the zeta potential was -56.7 ± 1.2 mV. The skin absorption rate of the nanoemulsion was compared with emulsion as a control. As a result of the nanoemulsion and general emulsion skin absorption test, the cumulative absorption of the nanoemulsion was 79.53 ± 0.23%, and the cumulative absorption of the emulsion as a control was 66.54 ± 1.45% after 24 h, which was 13% higher than the emulsion.