The solubility of pidotimod was measured by employing a dynamic equilibrium method in nine pure solvents [water, methanol, benzyl alcohol, ethanol, acetone, iso-propanol, nbutanol, acetonitrile, and N,N-dimethyl formamide (DMF)] and two binary solvents (methanol + acetone and methanol + butyl acetate) from 278.15 to 323.15 K, and mole fraction solubility of pidotimod increased with increasing measured temperature in all systems under atmospheric pressure. The mole fraction solubility of pidotimod in pure solvents is the highest in DMF and lowest in acetone. For the methanol + acetone binary solvent system, the solubility of pidotimod at the same temperature is higher than that in their neat solvents. In methanol + butyl acetate binary solvents, the solubility decreased with the increasing concentration of butyl acetate. The experimental solubility of pidotimod in the pure solvents was correlated with the Apelblat, Wilson, and NRTL models; it showed that the models agreed well with experimental data. Good correlation was also obtained by Wilson, NRTL, and CNIBS/ R−K models for binary solvents. The solute−solvent interactions in the pure solvents were investigated according to the linear solvation energy relationship using multiple linear regression analysis.