The holoparasitic genus Cistanche (Orobanchaceae) has been the most widely used and well known genus in traditional Chinese medicine for centuries. This is the first study that reports the phytochemical profile of Cistanche armena – an endemic species from Armenia and evaluates the composition and biological activity in relation to specific organs of the parasite (flowers vs stem with tuber) and its interaction with two host species: Alhagi maurorum (Fabaceae) and Salsola dendroides (Chenopodiaceae). We identified polyphenolic compounds using the UPLC-PDA-MS/MS method and quantified the antioxidative effects; inhibitory activities; polyphenol, nitrate III and nitrate V contents; ABTSradical dot+, DPPH, and FRAP activities; and colour parameters. A total of 28 polyphenolic compounds were tentatively identified. In C. armena, 9 compounds belonged to the phenylethanoid glycosides, mainly acteoside, B-hydroxyverbascoside and echinacoside, and in its hosts, 19 compounds belonged mainly to hydroxycinnamic acid and the flavanols. The profile of polyphenols in the host species was qualitatively and quantitatively different than the profile of the compounds in the parasite; this indicates the existence of a unique pathway of compound biosynthesis in the parasite. The colour and the amount and bioactivity of the polyphenolic compounds found in Cistanche were very diverse and depended on both the host plant and their location (organs) in the parasite. The stem and tuber of Cistanche hosted by Salsola had the highest polyphenol content, which was approximately 4 times higher than that in the stem and flowers of Cistanche individuals that parasitized A. maurorum. In addition, the stem and tuber of Cistanche that parasitized S. dendroides was characterized by the highest antioxidant activity (ABTSradical dot+, DPPH and FRAP) and high inhibitory activities. Conversely, the amount of polyphenols in the host Alhagi was 12 times higher than that in S. dendroides. These results highlight the importance of C. armena as a promising source of functional and bioactive ingredients (harvested from potential cultivation, not from natural endangered localities) and also draws the attention of future researchers to an important aspect regarding the parasite organ and the host's influence on the harvested material of various parasitic herbs.