Scrophularia striata Boiss. (Scrophulariaceae family), as an important medicinal plant, is one of the species native to western Iran. This perennial herbaceous plant has been traditionally used to cure various diseases, including eye and ear infections, inflammation, infectious wounds, colds, and boils, and is also used to treat bacterial, fungal, and viral infections in the world. Since the COVID-19 pandemic outbreak, Ongoing efforts are proceeding worldwide to develop an efficient vaccine and use approaches to find preventive measures and effective treatment. S. striata was introduced as a phenylethanoid glycosides (PhGs) source. S. striata functions as a resistant plant under various stresses. The essential mechanism in response to abiotic and biotic stress is the production of phenolic compound precursors, which eventually leads to PhG compound accumulation, especially acteoside, in this plant. Acteoside operates as a powerful antioxidant that scavenges excess ROS content in biological systems. The study purposed to evaluate the acteoside content in response to Pb stress of S. striata. HPLC analysis was employed to identify PhGs between the untreated and Pb-treated shoots plants with three gathering times (24, 48, and 72 hours). Our results indicated that acteoside increased significantly after 72h under Pb stress, and no significant difference was observed in other time courses. In general, S. striata is a good source of PhGs, especially acteoside, with application in the pharmaceutical industry.