Schisandra sphenanthera is an very important medicinal plant, and its main medicinal component is bioactive lignans, which has been developed over the years as an important cash crop in the central mountainous. The S. sphenanthera fruit has the characteristics of food and medicine homology, which is favored by the majority consumers, but the root, stem, and leaf are not fully used. Furthermore, the genetic characteristics of S. sphenanthera are rarely understood, thus hindering the study of functional genome and lignan biosynthesis. To better understand the lignan metabolic pathway, transcriptome and metabolome analysises were performed on four major tissues in S. sphenanthera. As a consequence, 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the abundance of unique unigenes was highest in roots (9, 703), and lowest in leaves (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of the lignan metabolic processes. In the different tissues, lignans were preferentially enriched in fruits and roots by the genes expression profiles related to lignan metabolism and lignan compounds relative content. Furthermore, schisandrin B was found to be an important compound in S. sphenanthera. According to WGCNA analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB8, bHLH3, and bHLH5 could be related to the accumulation of lignans in S. sphenanthera fruits, CCR5, SDH4, CYP8, CYP20 and ERF7 could be related to the accumulation of lignans in S. sphenanthera roots. In this study, the transcriptome sequencing and targeted metabolic analysis of lignins that will lay a foundation for further study of biosynthetic genes of lignin and other natural products in S. sphenanthera, and also provided a new idea for the rational utilization of different tissues of S. sphenanthera.