The formation of complexes with different ligands in the interlayer space of montmorillonite saturated in Na+, Mg2+, Ca2+, Co2+, Cu2+, Ni2+, Fe3+, and Cr3+ was studied. Acetone, acetonitrile, dimethyl sulfoxide, and trimethylphosphate were used as ligands, The nature of the complexes was studied by means of X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, microcalorimetry, and ab initio quantum mechanical methods. In all cases, the organic ligands penetrate into the interlayer space at room temperature, forming complexes stable in vacuum with the interlayer cations. The ligand-cation ratio depends on the valence of the saturating cation, The cation-ligand interaction in these complexes has an ion-dipole electrostatic nature. The complexes are formed by the direct interaction of the oxygen or nitrogen atom of ligand and the interlayer cation. Using the quantum mechanical approach, allow us to determine the disposition of the ligand in these complexes. In all cases, only one layer of ligands is present in the Stable complexes.