Pinellia ternata (Thunb.) Breit is a traditional Chinese medicine with important pharmacological effects. However, its cultivation is challenged by soil degradation following excessive use of chemical fertilizer. We conducted an experiment exploring the effects of replacing chemical fertilizers with organic fertilizers (OF) on the growth and yield of P. ternata, as well as on the soil physicochemical properties and microbial community composition using containerized plants. Six fertilization treatments were evaluated, including control (CK), chemical fertilizer (CF), different proportions of replacing chemical fertilizer with organic fertilizer (OM). Containerized P. ternata plants in each OF treatment had greater growth and yield than the CK and CF treatments while maintaining alkaloid content. The OM treatment had the greatest yield among all treatments, with an increase of 42.35% and 44.93% compared to the CK and CF treatments, respectively. OF treatments improved soil quality and fertility by enhancing the activities of soil urease (S-UE) and sucrase (S-SC) enzymes while increasing soil organic matter and trace mineral elements. OF treatments increased bacterial abundance and changed soil community structure. In comparison to the CK microbial groups enriched in OM were OLB13, Vicinamibacteraceae, and Blrii41. There were also changes in the abundance of gene transcripts among treatments. The abundance of genes involved in the nitrogen cycle in the OM has increased, specifically promoting the transformation of N-NO into N-NH, a type of nitrogen more easily absorbed by P. ternata. Also, genes involved in "starch and sucrose metabolism" and "plant hormone signal transduction" pathways were positively correlated to P. ternata yield and were upregulated in the OM treatment. Overall, OF in P. ternata cultivation is a feasible practice in advancing sustainable agriculture and is potentially profitable in commercial production.