Xiaofeng Liu, Minjun Han, Zichao Yang, Zherui Chen, Yao Zhang, Rongfa Guan
Background: Cistanche deserticola Y. C. Ma (C. deserticola) is a widely recognized medicinal and edible homologous plant. Phenylethanoid glycosides (PhGs), as its dominant bioactive components, are characterized by diverse chemical structures and prominent multi-target synergistic pharmacological activities. This review aims to systematically outline the structural characteristics, structure–activity relationships, and pharmacological mechanisms of typical PhGs from C. deserticola, so as to provide a scientific basis for their further development and application. Methods: A comprehensive literature review was performed. The structural features, structure–activity relationships, and multi-dimensional pharmacological mechanisms of representative PhGs, including echinacoside, verbascoside, and cistanoside A, were systematically summarized and analyzed. Results: PhGs exert anti-inflammatory, antioxidant, immunomodulatory, neuroprotective, antitumor, and hepatoprotective effects mainly by regulating multiple signaling pathways, such as NF-κB, MAPK, PI3K/Akt, and Nrf2/HO-1. These compounds display promising application potential in the prevention and amelioration of chronic inflammatory diseases, aging-related disorders including Alzheimer’s disease and osteoporosis, as well as oxidative stress-induced injury. Conclusions: PhGs from C. deserticola possess distinct pharmacological effects and broad application prospects. Future research should emphasize in-depth structure–activity relationship investigations, multi-component synergistic mechanisms, safety evaluation, and formulation design to enhance bioavailability, thus promoting the industrial development and application of PhGs.