The Xiaolangdi Reservoir is the second largest water conservancy project in China and the last comprehensive water conservancy hub on the mainstream of the Yellow River, playing a vital role in the middle and lower reaches of the Yellow River. To study the effects of the construction of the Xiaolangdi Reservoir (1997–2001) on the runoff and sediment transport in the middle and lower reaches of the Yellow River, runoff and sediment transport data from 1963 to 2021 were based on the hydrological stations of Huayuankou, Gaocun, and Lijin. The unevenness coefficient, cumulative distance level method, Mann-Kendall test method, and wavelet transform method were used to analyze the runoff and sediment transport in the middle and lower reaches of the Yellow River at different time scales. The results of the study reveal that the completion of the Xiaolangdi Reservoir in the interannual range has little impact on the runoff in the middle and lower reaches of the Yellow River and a significant impact on sediment transport. The interannual runoff volumes of Huayuankou station, Gaocun station, and Lijin station were reduced by 20.1%, 20.39%, and 32.87%, respectively. In addition, the sediment transport volumes decreased by 90.03%, 85.34%, and 83.88%, respectively. It has a great influence on the monthly distribution of annual runoff. The annual runoff distribution is more uniform, increasing the runoff in the dry season, reducing the runoff in the wet season, and bringing forward the peak flow. The runoff and Sediment transport have obvious periodicity. After the operation of the Xiaolangdi Reservoir, the main cycle of runoff increases and the second main cycle disappears. The main cycle of Sediment transport did not change obviously, but the closer it was to the estuary, the less obvious the cycle was. The research results can provide a reference for ecological protection and high-quality development in the middle and lower reaches of the Yellow River.