Reductive soil disinfestation (RSD) is an effective agricultural practice to eliminate soil-borne pathogens that heavily relies on the organic substrate used. However, the influences of combined application of organic residues on disinfestation efficiency, soil microbiomes, and their associated functional characteristics are still not well-characterized. In this work, four treatments, i.e., untreated soil (CK), RSD with 15 t ha(-1)sugarcane bagasse (SB), bean dregs (BD), and their combinations (1:1, SB+BD), were conducted to investigate their influence on disinfestation efficiency, microbial functional diversity, community diversity, and composition using Biolog analysis, real-time PCR, and high-throughput sequencing. The SB+BD treatment had synergetic effects on soil microbial activity, metabolic activity, and functional diversity with similar efficacy in pathogen elimination and soil salinization alleviation, as compared to the SB and BD treatments. Moreover, the SB+BD treatment distinctly altered the structure and composition of bacterial and fungal communities, especially enriched the core microbiomes associated with soil general functions such as organic decomposition and nitrate removal. The SB+BD treatment also strengthened the soil specific functions including disease suppression through the regulation of unique microbiomes. In addition, the microbial richness, diversity, and evenness were significantly higher in the SB+BD-treated soil as compared to the SB- and BD-treated soils. Taken together, RSD incorporated with organic residue combination not only efficiently restore the degraded soils, but also considerably improve soil functions, which may benefit to the health for the future plant generations.