Cyclic wetting and drying process of the reservoir area has been affecting the long term stability of the reservoir area at the bankside (due to the degradation in the physio-mechanical properties of the sandstone). To simulate this phenomenon, an experimental program was designed and executed on the layered sandstone brought from the Three Gorges reservoir area. The following points were noticed based on the laboratory results: (1) The degradation trends of the deformation and strength properties of the layer sandstone rock were very noticeable during the water-rock interaction. (2) Water plays a significant role in the softening and weakening of processes of the layered sandstone. The degradation in the physio-mechanical properties of layered sandstone was attributed to micro-structural changes. (3) The degradation in the mechanical properties of layered sandstone were mainly due to the dissolution of weak planes. The findings of this research provide a good basis for stability analysis of bank slope.