The L-phenylalanine solubilities in 12 pure solvents (water, ethanol, methanol, n-propanol, isopropanol, n-butanol, isobutanol, acetonitrile, 1,4-dioxane, acetone, methyl acetate, and ethyl acetate) were measured from 283.15 to 325.15 K at 101.2 kPa. The results indicated that the L-phenylalanine solubility increased with temperature. Powder X-ray diffraction pattern (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were used to identify and characterize the equilibrated solid-phase samples. The solubility behavior and the solute–solvent interaction of L-phenylalanine in each selected monosolvent were explored by the empirical solvents' polarity parameter (ET(30)), hydrogen bonding, cohesive energy density, molecular structure, viscosity, and Hansen solubility parameters (HSPs). To extend the application range of the results, the experimental solubility data were correlated to the modified Apelblat model and the Yaws model. According to the Akaike Information Criterion (AIC), the modified Apelblat model was found to be better for the correlation of the L-phenylalanine solubility.