[Objective] Soils in reservoir ablation zones undergo continuous deterioration of shear strength under repeated wetting-drying cycles, which may induce large deformation failure and even landslide hazards of reservoir bank slopes, thereby seriously threatening people’s lives and property as well as the safe operation of regional engineering facilities. However, quantitative analyses of the entire large deformation failure process of reservoir bank slopes under the deterioration of soil shear-strength parameters in ablation zones remain limited. [Methods] Taking the Baishuihe landslide in the Three Gorges Reservoir area as an example, this study constructed a large deformation analysis framework for reservoir bank slopes considering the deterioration of soil shear-strength parameters in the ablation zone based on the single-point two-phase material point method. Based on the deterioration data of soil shear-strength parameters obtained from laboratory wetting-drying cycle tests, the dynamic response and large deformation failure process of reservoir bank slopes under different numbers of wetting-drying cycles were quantitatively analyzed to reveal the influence of soil shear-strength parameter deterioration on the instability and failure process of bank slopes. On this basis, four mitigation measures, namely surface soil reinforcement, impermeable panel, anti-slide piles, and slope toe reinforcement, were compared to evaluate their prevention and control effects on the large deformation failure of reservoir bank slopes. [Results] The results show that reservoir bank slope deformation accumulates continuously with increasing wetting-drying cycles and exhibits obvious staged responses. The effects of soil shear-strength parameter deterioration on different parts of the bank slope exhibit spatial differences. The deterioration mainly promotes deformation development and the expansion of shear zones at the slope toe and in the middle and lower parts of the slope, while exerting a relatively limited influence on the deformation of the middle and upper soil mass. Among the four mitigation measures, the impermeable panel shows the best effect in controlling large deformation failure induced by wetting-drying cycle deterioration, followed by slope toe reinforcement and surface soil reinforcement, while anti-slide piles show the lowest prevention and control effect. [Conclusion] The large deformation analysis framework for reservoir bank slopes constructed in this study based on the single-point two-phase material point method can effectively reproduce the whole process of reservoir bank slope failure from local deformation accumulation to overall instability and failure under the deterioration of soil shear-strength parameters in the ablation zone. The results can provide a reference for whole-process risk assessment and prevention and control of reservoir bank slopes.