Spray freeze-drying (SFD) is an effective method for reducing the size of thermosensitive organic substances that are sparingly soluble in water. Despite the advantages of the method, its use has not yet become widespread. We aimed at studying SFD technique for metronidazole as a heat-sensitive active pharmaceutical ingredient for reducing its particle size and investigated the morphological and physical parameters of the modified drug.The obtained particles were crystalline in all cases and their sizes were two and one order of magnitude smaller using water or dimethyl sulphoxide solutions, respectively, as compared to the initial reference metronidazole. The particle size varied depending on the experimental parameters (atomization pressure, peristaltic pump speed), although, the operating parameters had a smaller effect on the size of the materials than the applied concentration of starting solution, regardless of the solvent. The as-prepared samples had a microcrystalline structure that is retained for a long time.