The genus Polygonatum is an essential resource for traditional Chinese medicine (TCM). To investigate the molecular mechanism of lignan biosynthesis in Polygonatum sibiritumRed and Polygonatum kingianum var. grandifolium, we performed transcriptomic and metabolomic analyses of these two plants. Seventeen lignans were detected a total of 17 lignans. Among them,Cycloolivil-6-O-glucoside,Matairesinol-4,4'-di-O-glucoside,5'-Methoxyisolariciresitnol-9'-O-glucoside,Syringaresinol,Syringaresinol-4'-O-glucoside,Isolariciresinol-9'-O-glucoside, dihydrodehydrodiconiferyl alcohol-4-O-glucoside, Pinoresinol and Eleutheroside E were reported in the genus Polygonatum for the first time. Transcriptome sequencing identified 75 genes related to the lignin biosynthesis pathway belonging to 12 classes of transcription factor families, among which genes from the SET, C2H2, and GARP-G2-like families were dominant in lignin biosynthesis. In addition, a family of transcription factors such as SET, GARP-G2-like, C2H2, Trihelix, SWI/SNF-BAF60b, PHD, FAR1, C3H, AP2/ERF-ERF, and BES1 were found to have essential roles in lignin biosynthesis by combined metabolome and transcriptome analyses. This study lays the foundation for an in-depth understanding of Polygonatum lignan biosynthesis and metabolic mechanisms. This has significant reference value for the future cloning of critical genes for lignans and the selection and breeding of Polygonatumgermplasm resources with high lignan content.