Multicomponent, one-pot, highly efficient, and environmentally adapted synthesis of some novel polysubstituted imidazoles by the use of various aldehydes, benzil, aliphatic, and aromatic primary amines and ammonium acetate in the presence of Fe3O4 nanoparticles as catalyst under solvent-free condition is explained. A highly efficient role of Fe3O4 nanoparticles as catalyst in this synthesis was shown. By this advantage, several polysubstituted imidazoles as pharmaceutical important molecules can be prepared in high yield and high purity. This method is very easy and rapid for the synthesis of imidazole derivatives. All products were deduced from their IR and NMR spectroscopic data. The Fe3O4 nanoparticles were characterized by powdered X-ray diffraction (XRD), transmission electron microscopy (TEM), and FT-IR spectroscopy.