In arid and semi-arid regions, plants are often subjected to severe environmental conditions such as salinity, drought and extreme temperatures. Halophyte species are salt-tolerant plants which are characterized by high physiological plasticity and are able to thrive under stressful conditions by developing adaptive responses including the synthesis of several bioactive molecules such as terpenoids, phenolic compounds, sterols, polysaccharides, carotenoids, vitamins and glycosides. These primary and secondary metabolites possess potent biological activities including antioxidant, antiviral, antimicrobial, anti-inflammatory, and anticancer ones and epidemiological research suggests that these compounds may help prevent several chronic diseases, such as diabetes, chronic inflammation, atherosclerosis and cardiovascular disorders. Because of their high content on these bioactive metabolites, halophytes may offer a valuable source of healthy products and could be used as functional foods and nutraceuticals. This chapter deals with the ethnopharmacological uses of two famous halohyte genus; Zygophyllum and Nitraria in traditional medicine and reviews recent investigations on their phytochemical compositions and biological activities.