Abstract: This study used locally domesticated and cultivated susceptible Polygonatum sibiricum as the material. Tissue separation, plate streak, morphological observation and molecular biology methods were used to isolate pathogenic microorganisms and identify their species characteristics. The pathogenicity of the isolated pathogenic microorganisms to healthy tissues of Polygonatum sibiricum was verifed, and biological control methods for Polygonatum sibiricum disease were explored by 9 Chinese medicinal materials and 5 endophytic bacteria of Polygonatum. The results show that among the 10 strains of bacteria and 6 strains of fungi isolated from Polygonatum sibiricum infected tissues, 3 strains of fungi BY-Z1, BY-Z3 and BY-Z4 have strong pathogenicity. After identification, they are Fusarium redolens, Fusarium solani and Minimedusa polyspora. Minimedusa polyspora is the first reported basidiomycetes isolated from Polygonatum sibiricum. Coptidis rhizoma has the strongest growth inhibition on BY-Z1, with an inhibition rate of 74.0%, followed by Angelica sinensis (28.9%). Coptidis rhizoma has the strongest growth inhibition on BY-Z3, with an inhibition rate of 66.0%, followed by mudan cortex (21.6%). Coptidis rhizoma has the strongest growth inhibition on BY-Z4, with an inhibition rate of 100.0%, followed by roots of madder (53.0%). Bacillus subtilis has inhibitory effects on pathogenic fungi BY-Z1, BY-Z3 and BY-Z4, while endophytic bacteria H3 and H4 of Polygonatum sibiricum have inhibitory effects on BY-Z1 and BY-Z4. H1 has a strong inhibitory effect on BY-Z4.