Experimental solubility data of D(-)-salicin in twelve neat solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, acetone, acetonitrile, 1,4-dioxance, ethyl acetate, and water) and four binary solvents (water + ethanol, water + acetone, water + isopropanol, and water + methanol) in the temperature range from 283.15 to 323.15 K under atmosphere pressure were determined using the gravimetric method. When the solvent composition was constant, a positive correlation of D(-)-salicin solubility with experimental temperature was found in all investigated pure and mixed solvent systems. At a given temperature, inflection points were found in the solubility curves for binary solvent systems as the mole fraction of water increased, which may be attributed to the cosolvency phenomenon. For the monosolvents, the solubility of D(-)-salicin may be affected by certain factors, such as polarity, steric effects, dipolaritypolarizability, hydrogen bonds, and so on. The KAT-LSER model was used to perform the multiple linear regression analysis on pure and mixed solvent systems to reveal the solutesolvent and solventsolvent interactions. Finally, the modified Apelblat model, the JouybanAcree model, and the ApelblatJouybanAcree model were utilized to correlate the solubility data.