The determination of solubility of domperidone in aqueous cosolvent mixtures of isopropanol, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and ethanol was carried out by a shake-flask method over the temperatures from 293.15 to 333.15 K under local atmospheric pressure p = 101.1 kPa. It may be observed that the domperidone solubility increased and then decreased as the mass fractions of DMF (DMSO, isopropanol, or ethanol) increased. The maximum solubility data was found with the cosolvent composition of 0.8 in mass fraction. The determined solubility values were correlated using the Jouyban-Acree, van't Hoff-Jouyban-Acree, and Apelblat-Jouyban-Acree models. The attained average relative deviations were smaller than 7.56%. Preferential solvation analysis of domperidone was performed by the inverse Kirkwood-Buff integral method. The preferential solvation parameters (delta x(1,3)) by the cosolvent showed positive values in the composition regions of 0.20 < x(1) < 0.50 for DMF, 0.24 < x(1) < 0.55 for isopropanol, 0.20 < x(1) < 0.45 for DMSO, and 0.24 < x(1) < 0.61 for ethanol. Domperidone was solvated preferentially by the cosolvents in these regions. We may conjecture that the drug acts as a Lewis acid in the presence of isopropanol (DMF, DMSO, and ethanol) molecules.