The study aimed to investigate the solubility and thermodynamic properties of ivermectin in two binary solvent mixtures including (1-propanol + water) and (2-propanol + water). The study was conducted over a temperature range of 293.2–313.2 K. Ivermectin solubility was found to increase with temperature in both solvent systems, with higher solubility values observed at elevated temperatures and in mixtures containing 0.8 mass fraction of 1-propanol and 2-propanol. Furthermore, comparative analysis revealed that the solubility of ivermectin was significantly higher in mixtures composed of 1-propanol and water compared to those comprising 2-propanol and water. In order to analyze the experimental solubility data, a variety of linear and nonlinear models was utilized and subsequently their mean relative deviations (MRD%) to the experimental values was compared to assess their effectiveness. Computed MRD% lower than 27% demonstrated promising results in predicting and describing ivermectin solubility in binary mixtures. Additionally, the study calculated apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy, using the van’t Hoff and Gibbs equations. Thermodynamic analysis indicates that ivermectin dissolves readily in both mixtures due to a decreased Gibbs free energy, increased entropy, and heat absorption during dissolution.