NAC (NAM, ATAF1/2 and CUC2) transcription factors (TFs) are a class of TFs families unique to plants, which not only play an important role in the growth and developmental stages of plants but also function in response to stress and regulation of secondary metabolite biosynthesis. However, there are few studies on NAC genes in the medicinal plant Isatis indigotica. In this study, 96 IiNAC genes were identified based on the whole-genome data of I. indigotica, distributed in seven chromosomes and three contigs. IiNAC genes were structurally conserved and divided into 15 subgroups. Cis-elements were identified in the promoter region of the IiNAC gene in response to plant growth and development, abiotic stresses and hormones. In addition, transcriptome and metabolome data of I. indigotica leaves under salt stress were analyzed to construct a network of IiNAC gene co-expression and metabolite association. Ten differentially expressed IiNAC genes were co-expressed with 109 TFs, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that most of these genes were associated with plant growth and development and abiotic stress responses. Eleven IiNAC genes were positively associated with 72 metabolites. Eleven IiNAC genes were positively or negatively associated with 47 metabolites through 37 TFs. Commonly associated secondary metabolites include two terpenoids, abscisic acid and bilobalide, two flavonoids, dihydrokaempferol and syringaldehyde, a coumarin, 7-methoxycoumarin, an alkaloid, lupinine, and quinone dihydrotanshinone I. This study provides important data to support the identification of the NAC gene family in I. indigotica and the regulatory functions of IiNAC genes in metabolites under salt stress. © 2023