An efficient method for the synthesis of 3,4-disubstituted isoxazol-5(4H)-one derivatives catalyzed by magnetic deep eutectic solvent is reported. The structure of the nano-catalyst was characterized by FE-SEM, FT-IR, EDX, and TGA. The excellent activity of the catalyst was displayed for the synthesis of 3,4-disubstituted isoxazol-5(4H)-one derivatives. This heterogeneous catalyst can be easily recovered via a magnetic field and reused for subsequent reactions. Easy workup, high yields in a short time, and a non-toxic catalyst are the main merits of this method.