Solubilities of carvedilol (CVD) in binary mixtures of (ethanol + propylene glycol (PG)) at 298.2, 303.2, 308.2, and 313.2 K are reported. The modified versions of the van't Hoff and Gibbs equations were used to calculate the thermodynamic properties (enthalpy (ΔH°), entropy (ΔS°), and Gibbs energy (ΔG°) standard changes of solutions) for CVD dissolved in (ethanol (1) + PG (2)) mixtures from the solubility data. The solubility data of CVD in (ethanol (1) + PG (2)) at different temperatures were correlated using different mathematical models, i.e., the Jouyban–Acree model, a combination of the Jouyban–Acree model with the van't Hoff model, and two modified versions of the Jouyban–Acree model. Solubility data of seven drugs in (ethanol (1) + PG (2)) at different temperatures were used to develop a quantitative structure–property relationship model for predicting solubility in solvent mixtures. In addition, enthalpy–entropy compensation using ΔH° vs ΔG° and ΔH° vs TΔS° which explains the mechanism of cosolvency at different temperatures was discussed.