Dexamethasone is a glucocorticoid drug used for the treatment of acute and chronic inflammatory conditions, autoimmune diseases, some cancers, and several other pathologies. It is widely marketed worldwide especially under solid dosage forms. This study aimed to assess its compatibility with solid pharmaceutical excipients. Compatibility study was conducted through the preparation of binary mixtures (1:1, w/w) of dexamethasone with 12 selected excipients. Binary mixtures were analyzed by thermoanalytical techniques (thermogravimetric and differential thermal analysis), Fourier transform infrared spectroscopy, and X-ray diffraction. TG curves pointed only slight anticipations of dexamethasone decomposition. DTA curves showed interactions signs with microcrystalline cellulose 101 and 102, magnesium stearate, mannitol, and polyvinylpyrrolidone. Drug infrared absorption profile was not affected by the mixture with most excipients. X-ray diffractograms of all binary mixtures did not exhibit signs of interactions with changes of dexamethasone crystalline state. These results pointed that the interactions found by DTA technique were probably heat-induced. Therefore, the above-mentioned excipients should be carefully used in solid dosage forms with heat-based manufacturing processes.