The mixture of water, methanol, and ethanol is frequently produced in the pharmaceutical industry. To separate the mixture by extractive distillation, the selection of entrainer is a crucial step. Entrainer performances of ethylene glycol (EG) and some mixed solvents were evaluated in this work, including EG + KOAc, EG + CaCl2, EG + LiCl, and EG + choline chloride (ChCl). Isobaric vapor-liquid equilibrium data were measured for the quaternary and quinary systems at 101.3 kPa and were modeled by use of the NRTL equation. The effects of EG and the mixed solvents on the relative volatilities of the volatile key components are discussed in relation to the effects on the activity coefficients. Results showed that adding salts into ethylene glycol results in significant improvement of solvent performance. A more rapid decrease in the activity coefficient of water, as well as an increase in the activity coefficient of ethanol, can be observed with the addition of the mixed solvents, resulting in a more rapid increase in the relative volatility of ethanol to water. The mixed solvent EG + ChCl 4:3 showed the best performance, having a value of 5.85 for the relative volatility of ethanol to water at a solvent mass fraction of 0.8.