Despite being of paramount importance for developing the biorefinery concept and being a highly versatile building block to synthesize a plethora of biobased molecules, experimental data on the solubility of sorbitol in pure organic solvents and heat capacity data are scarce. This work reports the solubility of the stable γ polymorph of sorbitol in eleven organic solvents of polar protic and polar aprotic nature within the range of temperature 298–338 K using a gravimetric method. No solution-mediated polymorphic transformation was detected during equilibration as confirmed by PXRD. Moreover, the solid sorbitol is characterized by TGA, DSC, FTIR, SEM and optical microscopy. Molar fraction solubility data has been modelled using empirical, semiempirical and mechanistic-based rigorous thermodynamic analysis approaches, providing thus expressions of practical usefulness to interpolate and extrapolate solubility data. In addition to the melting point and melting enthalpy, the heat capacity dependence upon temperature is determined experimentally for the pure solid, the pure liquid and the supercooled melt. Such data is used to estimate the sorbitol activity coefficients in the studied solvents at different temperatures, revealing strongly positive deviations with respect to ideality, i.e. weaker solute–solvent interactions than solute–solute. The rank of solubility obtained shows: (i) that sorbitol is soluble in all the studied solvents, yet to different extent, (ii) a higher solubility for proton donor solvents, which increases upon branching and decreases with increasing molecular size, and (iii) polar aprotic solvents can exploit the benefits from H-bonding but these languish with increasing size of the alkyl groups attached to the carbonyl group. Finally, molecular dynamics simulations are used to compute solvation free energies, which are ultimately correlated to the rank of solubility observed and underline H-bonding as the most prominent interaction governing solubility. A comprehensive discussion on the H-bonding relevance from Hansen solubility parameters as a function of the studied polar solvents protic/aprotic nature, and the size related role of non-polar moieties in solvents molecules is provided, contributing to enhance our knowledge on the solid–liquid equilibria governing interactions of polysaccharide-organic solvents systems.