In this paper, we report the facile preparation of monodisperse titanium dioxide-diltiazem/tetrachlorobismuth core-shell nanospheres (TiO2@DTMBi), in which, diltiazem (DTM)/tetrachlorobismuth (BiCl4) complexes were employed as electroactive materials. The morphology, size, formation, and structure of the obtained TiO2@DTMBi spheres were investigated by transmission electron microscopy, scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray diffraction. The optimal condition of obtained monodisperse 40-nm TiO2@DTMBi spheres was researched. The results of using TiO2@DTMBi nanospheres as proposed drug sensor indicate a wide linear range (10-7 to 10-1 M) and a very low detection limit of 0.20 μg/mL.