Soil contamination by toxic metals and metalloids poses a grave threat to food security and human well-being. Immobilization serves as an effective method for the remediation of soils contaminated by metal(loid)s. Nevertheless, the ability of soil amendments for simultaneous immobilization of cations and oxyanions, and the long-term effectiveness of immobilization need substantial improvements. In this study, we used a series of layered double hydroxides (LDHs), including Mg-Al LDH and Ca-Al LDH fabricated from pure chemicals, and one waste-derived LDH synthesized using granulated ground blast furnace slag (GGBS), for the immobilization of Cu, Zn, As, and Sb in a historically contaminated soil obscured from a mining-affected region. The LDHs were first subjected to iron (Fe) modification to enhance their short-term immobilization performances toward metal(loid)s. Furthermore, the long-term effectiveness of Fe-modified LDHs was examined via two sets of experiments, including column experiments simulating 2-year water leaching, and accelerated aging experiments simulating 100-year proton attack. It was observed that Fe-modified LDHs, either made from pure chemicals or GGBS, demonstrated promising long-term immobilization performances toward metal(loid)s. Results from this study are encouraging for the future use of LDHs for simultaneous and long-term immobilization of metal(loid)s in soil.