Abstract: To study the effect of different mineral compositions and microstructures on the weakening of metamorphic rock macroscopic physical and mechanical parameters during wetting-drying cycles, wetting-drying cycle tests were conducted. The evolution mechanism and mutual relationship of macroscopic physical and mechanical parameters with the microscopic mineral composition and structure of metamorphic sandstone were investigated. The results show that the physical and mechanical parameters of the rock decrease with an increase in the number of wetting-drying cycles, and the decrease ratio slows down with an increase in the number of cycles. Uniaxial compressive tests of rock samples after cycling demonstrate that the initial crack compaction phenomenon appears in the stress-strain curve and becomes more obvious with an increase in the number of cycles. The failure characteristics of rock samples change from shear failure to tensile failure with an increase in the cycle numbers. Combined with XRD and SEM tests, the changes in mineral composition and microscopic pore area are statistically analyzed. It is concluded that the hydration and dissolution of chlorite, mica, plagioclase, and the hydration and expansion of microscopic pores are the main reasons for rock damage. Therefore, the concepts of mineral composition degradation degree(D_m) and microstructure degradation degree(D_c) are proposed to quantify rock water-rock cycle microscopic damage, and a regression model for the weakening of rock physical and mechanical parameters under the influence of mineral composition and microstructure under the water-rock cycle is established. The proposed model provides a reference for predicting the value of rock physical and mechanical parameters under various wetting-drying cycle numbers.