In order to investigate the influence of calcium silicate hydrate (CSH) gel-montmorillonite interface energy on unconfined compressive strength of cement-stabilized montmorillonite clay, the energy of the interface area between montmorillonite and CSH was quantitatively calculated by molecular dynamics simulation method. Then, combining with the grey correlation degree analysis and X-ray diffraction (XRD), the correctness and deviation sources of the model were discussed. The results show that the CSH-montmorillonite interface energy consists of van der Waals force, hydrogen bonding energy and electrostatic interaction. There is a good correlation between the CSH-montmorillonite interface energy and unconfined compressive strength of cement-stabilized montmorillonite clay. The interface energy decreases with the increase of water molecules, and decreases first and then increases with the increase of montmorillonite layers. At the CSH-montmorillonite interface, the repulsive force can be maximized or the gravitational force can be minimized by adjusting the water-to-cement ratio and the cement-to-soil ratio to obtain an optimal unconfined compressive strength of the cement-stabilized montmorillonite clay.