The stability and electronic structure of the possible Janus phase for the representative example of transition metal trichalcogenide FePS1.5Se1.5 crystals are studied and discussed. The respective stoichiometric layered parent (FePS3 and FePSe3) and mixed (FePS1.5Se1.5) compounds are successfully synthesized, and our experimental data confirm the high quality of the obtained crystals and the uniform random distribution of S and Se atoms in the chalcogens’ layers for the FePS1.5Se1.5 crystals. These results are supported by the detailed density functional theory calculations, which indicate the absence of the Janus phase for the layered 3D FePS1.5Se1.5. This effect is explained by the large uncompensated dipole moment for the Janus phase, and the possible routes for the stabilization of 2D FePS1.5Se1.5 Janus layers are discussed.