To explore the remediation effects of mercaptopalygorskite on cadmium (Cd)-arsenic (As) co-contaminated soil and its microbial community, in this study, 1% and 2% mercaptopalygorskite were applied to Cd-As co-contaminated paddy soil to explore their effects on soil properties, the availabilities of Cd and As. High-throughput sequencing technology was also used to explore the effect of mercaptopalygorskite on microbial community. The results showed that the addition of mercaptopalygorskite significantly reduced soil pH, and the effect was more obvious under 2% mercaptopalygorskite treatment. Compared with the control, soil organic matter contents increased significantly by 30.2% and 60.9% under 1% and 2% mercaptopalygorskite treatments, respectively, the concentration of available Cd and toxicity characteristic leaching procedure (TCLP) of Cd reduced by 97.7%-98.3% and 77.1%-92.7% under 1% and 2% mercaptopalygorskite treatments, respectively. Whereas the concentration of available As changed insignificantly. Furthermore, the addition of mercaptopalygorskite had no significant effect on soil microbial diversity and richness, however, the relative abundance of Pseudanabaena_NgrPSln22 and Pseudomonas genuses decreased by 85.4%-98.1% and 75.3%-78.9%, respectively. Mercaptopalygorskite addition significantly altered soil microbial community structure, with pH and Cd availability being the main factors affecting microbial community structure. In conclusion, mercaptopalygorskite can not only significantly reduce the availability of Cd and promote soil organic matter content, but also impact soil microbial community structure and increase the abundance of disease-resistant bacteria and reduce the abundance of azotobacter.