Nanoparticles are key focus of research for a wide range of novel applications. As such, ZnFe2O4 magnetic nanoparticles were synthesized hydrothermally and characterized via scanning and transmission electron microscopies, powder X‐ray diffraction, energy‐dispersive X‐ray and infrared spectroscopies, thermogravimetric analysis and magnetic measurements. They were used as a robust catalyst for the synthesis of a series of biologically active multi‐substituted imidazoles using a multicomponent reaction by the reaction of benzil with various aromatic aldehydes, ammonium acetate and aliphatic amines (N,N‐dimethyl‐1,3‐propanediamine and 1‐amino‐2‐propanol) under solvent‐free conditions. The key advantages of this method are shorter reaction times, very high yield and ease of operation. The thermally and chemically stable, benign and economical catalyst was easily recovered using an external magnet and reused in at least five successive runs without an appreciable loss of activity. All of these novel synthesized compounds were characterized from spectral data and their purities were checked using thin‐layer chromatography, giving one spot. Furthermore, the prepared compounds were tested for their anti‐inflammatory activity.