Remediation materials are the most critical factors for in situ immobilization of soil contaminated by heavy metals. In this study, in order to improve the performance of palygorskite (Pal), a new remediation material, mercapto-grafted palygorskite (MPal) was synthesized by grafting mercapto groups onto the surface of Pal. The results of field application in northern China showed that at a dosage of 0.12–0.23 kg m⁻², MPal significantly reduced the available concentrations of Cd, Pb, and Cr in the soil by 52.2%, 29.9%, and 46.2%, respectively. Concurrently, Cd, Pb, and Cr concentrations in the shoots of head lettuce also decreased significantly, with the highest reduction being 44.0%, 61.5%, and 50.0%, respectively. At the same dosage, MPal had a better immobilization effect than Pal. There was no significant change in the pH of the vegetable soil, while the zeta potential decreased significantly, indicating that the MPal did not immobilize the heavy metals by increasing the pH, making it suitable for alkaline farmland soil. In addition, soil environmental quality was improved overall. MPal increased the activities of urease, β-glucosidase, cellulase, and catalase by 15.4%, 56.5%, 7.8%, and 14.9%, respectively. It increased the number of fungi and actinomycetes by 4.5% and 23.1%, respectively. MPal, as a new remediation material for soil contaminated by heavy metals, could achieve efficient remediation effects when applied in small doses. Compared with Pal, it is environmentally friendly, is low cost, and is more suitable for the treatment of heavy metal pollution in large areas of farmland.