Replant failure has threatened the production of Sanqi ginseng (Panax notoginseng) mainly due to the accumulation of soil-borne pathogens and allelochemicals. Reductive soil disinfestation (RSD) is an effective practice used to eliminate soil-borne pathogens; however, the potential impact of RSD on the degradation of allelochemicals and the growth of replant Sanqi ginseng seedlings remain poorly understood. In this study, RSD was conducted on a Sanqi ginseng monoculture system (SGMS) and a maize-Sanqi ginseng system (MSGS), defined as SGMS_RSD and MSGS_RSD, respectively. The aim was to investigate the impact of RSD on allelochemicals, soil microbiomes, and survival rates of replant seedlings. Both short-term maize planting and RSD treatment significantly degraded the ginsenosides in Sanqi ginseng-cultivated soils, with the degradation rate being higher in the RSD treatment. The population of Fusarium oxysporum and the relative abundance of genus Fusarium were dramatically suppressed by RSD treatment. Furthermore, the RSD treatment, but not maize planting, markedly alleviated the replant failure of Sanqi ginseng, with the seedling survival rate being 52.7-70.7% 6months after transplanting. Interestingly, RSD followed by short-term maize planting promoted microbial activity restoration, ginsenoside degradation, and ultimately alleviated the replant failure much better than RSD treatment alone (70.7% vs. 52.7%). Collectively, these results indicate that RSD treatment could considerably reduce the obstacles and might also act as a potential agriculture regime for overcoming the replant failure of Sanqi ginseng. Additional practices, such as crop rotation, beneficial microorganism inoculation, etc. may also still be needed to ensure the long-term efficacy of seedling survival.