Abstract: The intermediary weathered sandstone of a slope in the Three Gorges Reservoir area is taken as the research object when investigating the damage and degradation of rock under periodic wetting-drying cycles. The full section CT scan, Brazil disk split tests and uniaxial compression tests on sandstones under different wetting-drying cycle times (n) are performed respectively. The results show that the macro mesoscopic mechanical parameters of dry sandstone are greater than those of wet sandstone under the same wetting-drying cycle times. The mean values of CT numbers in typical areas nonlinearly and cumulatively increase with the increase of wetting-drying cycle times. They change faster initially, and the mesoscopic damage evolution rate tends to slow down when the wetting-drying cycle times exceed three. The uniaxial compressive strength, elasticity modulus, tensile strength, cohesion and internal friction angle of sandstone decrease logarithmically with the increase of wetting-drying cycle times, while the Poisson's ratio of sandstone increases as the wetting-drying cycle times increase. The role of wetting-drying circulation on deterioration degree of different mechanical parameters of sandstone is variant. The sensibility of tensile properties of sandstone specimen to water is greater than that of compression properties of sandstone one. The M-C yield criterion of sandstone under dry and wet conditions is corrected respectively based on the data regression analysis, thus providing a theoretical basis for the breaking strength acquisition of rock under arbitrary confining pressure.