This study aims to investigate the polymorphism, physical stability, and amorphization possibilities of dexamethasone (DEX) drug. Milling was found to be an advantageous mean to prepare amorphous DEX nonchemically degraded. It appears to be a very useful process that allowed generating crystalline polymorphic transformation, either from the milling induced amorphous sample or from a mechanically damaged polymorphic form. The paper illustrates the interest of milling as a complementary tool to screen crystal polymorphism and to determine the relative stability of polymorphs when the decision is difficult. Physical characterizations were mainly carried out using X-ray diffraction and differential scanning calorimetry.