Background Artemisia plants are widely distributed in East Asia. Though the Artemisia cultivars are commonly used as raw materials of medicine, food or moxibustion in China, most of the potential medical and nutritional ingredients, especially flavonoids ingredients are largely unknown, which imped further utilization of these cultivars.Results In this study, two Artemisia cultivars usually used as the source of moxibustion or food, named NYSY and NYYY were investigated. NYSY and NYYY were authenticated as A.argyi based on molecular data. In all detected 882 metabolic ingredients, nearly half of biological ingredients varied between two cultivars. Most of potential medical ingredients, especially flavonoids (flavone, flavonol, isoflavone, and anthocyanin) were up regulated in NYYY. The contents of total flavonoids and their antioxidant activities were also higher in NYYY. In addition, transcriptional evidences showed that more than half of flavonoids synthesis genes were up regulated in NYYY, and their putative transcription factors members of MYB, bHLH, bZIP, WRKY, NAC and MADS families were uncovered.Conclusions In all, our results provide metabolome and transcriptome evidence to underly the biochemical ingredients, especially flavonoids variation in two Artemisia cultivars. This study provides scientific evidence for the utilizing and improving the quality of Artemisia cultivars in the future.