Developing high-performance solvents for extraction and optimizing process technologies is crucial for efficient extractive distillation (ED) separation of azeotrope mixtures. In this paper, computer-aided screening was used to study the ED of azeotrope mixtures in ethyl acetate and ethanol systems using organic solvent dimethyl sulfoxide (DMSO) and ionic liquid (IL) ([EMIM][Ac]). The structural relationship between the ILs and the azeotrope mixture was analyzed by σ-profile, molecular surface electrostatic potential, interaction energy, and separation gradient. Subsequently, process simulation was carried out using Aspen Plus software and global optimization was performed with genetic algorithm, which found that both traditional organic solvents and ILs have good separation effects. But considering the high volatility of organic solvents and low saturation vapor pressure of ILs, it is considered to combine them to further explore the cost and carbon emission advantages in extractive distillation separation. Compared with pure organic solvent and pure ILs separation processes, the TAC of the process using an IL-based mixed solvent process decreased by 5.11 and 21.98%, respectively. The carbon emissions of the mixed extractant process were slightly higher than those of the pure organic solvent process, but the addition of ILs made very little volatilization of organic solvents, saving a charge for extractant use. By improving the process, waste heat is effectively recovered, which can save most of the utility engineering costs, and compared with the previous process, the total alkali consumption and carbon dioxide emissions are reduced by 9.43 and 27.17%, respectively. This exploration provides a theoretical reference for the development application and industrial research of ED processes using IL-based mixed solvents.