Root rot diseases are prevalent in many Coptis chinensis Franch. production areas, perhaps partially due to the overuse of synthetic fertilizers. Synthetic fertilizers can also lead to soil degradation. Trichoderma is widely used in biofertilizers and biopesticides. This study applied a combination of four Trichoderma species (compound Trichoderma agent, CTA) to C. chinensis and evaluated its effects on growth, as well as rhizosphere soil nutrients, enzyme activities, and microbial community structure. The purpose of this study was to estimate the potential of using CTA as a biofertilizer for C. chinensis, and determine if it could, at least partially, replace synthetic fertilizers to control root rot disease and maintain soil fertility. CTA, compound fertilizer and sterile water were applied to C. chinensis plants. After 60 days, the soluble sugar, soluble protein, chlorophyll of leaves, and individual weight of each plant were measured. The rhizosphere soil nutrient content, enzymatic activity, and the microbial community were also determined. The results were analyzed to evaluate the effect of CTA on C. chinensis growth and soil fertility. CTA increased the soluble protein, chlorophyll, and individual weight of C. chinensis plants while compound fertilizer decreased chlorophyll. CTA increased the activities of urease and catalase in rhizosphere soil, whereas the compound fertilizer decreased urease, catalase, and alkaline phosphatase activities. CTA elevated soil pH, while compound fertilizer reduced it. CTA had no significant effects on soil nutrients and organic matter. CTA decreased the fungal number and alpha-diversity of fungi and bacteria, and both the fungal and bacterial communities were significantly different from the other two. CTA increased B/F value, which improved the rhizosphere microbial community. Both CTA and the compound fertilizer significantly altered the soil microbial community. The relative abundance of Ascomycota was higher and Basidiomycota was lower after CTA treatment than after the other two treatments, indicating that the soil treated with CTA was healthier than that of the other two treatments. CTA decreased harmful Ilyonectria mors-panacis and Corynebacterium sp. And increased beneficial Ralstonia picketti. Trichoderma spp. could exist in C. chinensis rhizosphere soil for a long time. The functional prediction results demonstrated that CTA reduced some rhizosphere phytopathogenic fungi. Correlation analysis showed that CTA elevated rhizosphere pH and enzyme activities. In summary, synthetic fertilizers damaged soil fertility, and the overuse of them might be responsible for root rot disease, while CTA could promote C. chinensis growth, improve soil and decrease the incidence and severity of C. chinensis root rot disease. Therefore, as a biofertilizer, CTA can, at least partially, replace synthetic fertilizers in C. chinensis production. Combining it with organic fertilizer will increase the potential of Trichoderma.