In the current study, some of the physiological adaptive responses were evaluated in five true xerophytic plants, for their medicinal importance; Ephedra alata Dence., Lycium shawii Roem., Nitraria retusa (Forssk.), Ochradinus baccatus Del. and Tamarix nilotica (Ehrenb.) growing naturally (wild plants) at Wadi Hof represented by site 1(drought stress) and Red sea coast represented by site 2 (salinity stress). The selected plants were collected during spring and autumn seasons of the studied year (2019). The results revealed that the enzymatic activities of catalase, peroxidase, polyphenol oxidase and superoxide dismutase for the studied plants were higher in spring season compared to the autumn one and the highest activity of these enzymes were represented in O. baccatus inhabiting site (1). DNA content in most studied plants was increased during spring season and the highest value was recorded in L.Shawii inhibiting site (1). Additionally, the highest value of RNA was observed in N.retusa grown at site (2) during autumn season. Results showed that, the highest values of total phenols content of E.alata and T.nilotica were obtained during autumn season at site (1). While the lowest value of total phenols content of O.baccatus was achieved in the site (2) during spring season. The studied plants grown at site(2) possessed a highly significant increment in total flavonoids content during autumn season and the highest value was recorded in T.nilotica .On the contrary, the lowest value of total flavonoids was recorded in O.baccatus located at site ( 2) during spring season. Data showed that the methanol extracts of T. nilotica plant grown at two studied sites during the selected seasons showed the highest antimicrobial activity against all tested bacterial and fungal strains compared to other tested plants.