The structures, spectral properties and molecular orbitals of six nonsymmetrically substituted uranyl–salophen complexes were investigated using density functional theory calculations. The results indicated that the complexes were more stable than the ligands. Phenolic hydroxyl groups were able to form hydrogen bonds with the N atoms in the ligands, which greatly impacted both on IR and NMR spectra. For an absolute configuration of “∨“, a positive absorption peak emerged first, then a negative absorption peak followed in the ECD spectra of uranyl–salophen in the range of 250–500 nm. This study thus provided a theoretical basis and guidance for the design and synthesis of uranyl–salophen with desirable functions.