The impoundment of the Three Gorges Reservoir in China inevitably caused the reservoir landslides to develop toward instability, which has attracted widespread attention. Taking the Huangtupo Riverside Slump 1# with the structural characteristics of double sliding zones as a case, this study focuses on the sliding zone soils in the hydro-fluctuation belt affected by the periodic fluctuations of reservoir water level. The wetting-drying cycles test is carried out to simulate the cyclic impact of the fluctuations on the sliding zone soils. Hence the weakening law of the strength parameters is illustrated and well characterized by an exponential function model. Considering the different number of wetting-drying cycles, the long-term reliability of the shallow and deep sliding surfaces is quantified via the imbalance thrust force method and reliability theory. The results indicate that the local failure probability of both sliding surfaces gradually rises as the number of wetting-drying cycles increases. In particular, the shallow sliding surface presents a greater local failure probability than that of the deep one since more slices are in the hydro-fluctuation belt. Besides, the sensitivity of the landslide response to the strength parameters is different, and the internal friction angle is much greater than the cohesion. The area of the hydro-fluctuation belt plays a significant role on the long-term reliability of the landslide, which should be closely monitored to guide the reservoir operation.