The physico-chemical characterization of the polymorphs of nateglinide (named B, H and S), an antidiabetic agent, has been performed by means of thermal, diffractometric, spectroscopic and electron microscopic measurements. It has been established that S polymorph can crystallize from the melt obtained from both B and H samples or also following an isothermal treatment of both forms at temperatures lower than the relevant melting points. By X-ray diffraction it could be shown that the three polymorphs have different crystal structure. On the other hand the indication has been drawn from IR spectra that the molecular structure of B is sensibly different from those of H and S forms that have a very similar molecular structure. Finally, the microstructure features of the three polymorphs have been examined by scanning electron microscopy. Our analyses have allowed to evaluate the relative stability of the three polymorphs through the construction of the energy vs. temperature diagram. In particular, S polymorph, the highest-melting form, has resulted to be the only stable form, while the B and H forms are metastable.