Abstract: Sediments are complex mixtures, and different geological studies often require the extraction of different chemical components from sediments. Sequential leaching is a commonly used method to differentiate different components of sediments. However, the effectiveness of sequential leaching experiments conducted so far is often explored only for a single type of sediment sample. It is unclear whether the leaching effect is also widely applicable to other types of sediment samples. In this study, three types of sediment samples from the Yangtze River, the Loess Plateau, and the South China Sea were selected. Three methods, including two commonly used sequential leaching procedures and an improved procedure proposed in this study, were applied to leach the samples. The aim was to assess the impact of different leaching methods on the REE and Sr-Nd isotopes analysis of the sediment detrital components. Results show that 1.5 M hydrochloric acid tends to excessively remove carbonate components from the samples, leading to a loss of over 50% of some major elements (Mn, Fe, and Mg) and REE elements. It could also cause the dissolution of some silicate detrital components, including clay minerals. 1 M sodium acetate buffer solution with moderate acidity was shown more favorable for accurately removing carbonate components from all sediments. The removal of non-detrital components resulted in an increase of Sr isotopes in all the sediments. The main component influencing the isotopic composition of Sr in detrital components was the carbonate fraction. For Nd isotopes, the removal of non-detrital components led to a decrease in ɛNd of sediment detrital components by 1—2 units. However, the relationship between the loss of Nd and the changes in detrital component ɛNd is more complex, and the effects of excessive shaking and prolonged reaction time on the ɛNd of different types of sediments still require further investigation.