This work focuses on the experimental measurement and modeling of solid–liquid equilibria containing continuous binary solid solutions crystallized from solvent mixtures for the usage in antisolvent crystallization. The newly constructed quaternary phase diagrams of l-valine/l-leucine in water/2-propanol and water/acetone systems are analyzed and compared to those of water/ethanol mixtures. Experimental data sets are determined via high-performance liquid chromatography, while the formation of solid solutions is confirmed with powder X-ray diffraction. Our validated modeling approach for the ternary l-valine/l-leucine/water mixture is extended to the aforementioned quaternary systems. The modeling combines the Perturbed Chain-Statistical Associating Fluid Theory and the Non-Random Two-Liquid model to describe the liquid and solid phases, respectively. Additionally, two modeling approaches (predictive and semi-predictive) are proposed. Both models show good agreement with the experimental solubility data sets of the binary solutions. However, larger deviations were observed in three- and four-component systems, especially toward the solubility maxima. Therefore, the modeling approach should be used for qualitative initial antisolvent screenings for the separation of solid solutions using counter-current crystallization.