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Due to their robust antioxidant capabilities, potential health benefits, wide variety of biological activities, and strong antioxidant qualities, phenolic compounds are substances that have drawn considerable attention in recent years. The main goal of the review is to draw attention to saharian Algerian medicinal plants and the determination of their bioactivity (antioxidant, anti-cancer, and anti-inflammatory importance), and to present their chemical composition as well as in vivo and in vitro studies, clinical studies, and other studies confirming their real impact on human health. Research results have revealed a rich variety of medicinal plants used to treat various disease states in this region. Based on in vivo and in vitro studies, biological activity, and clinical studies, a list of 34 species of desert plants, belonging to 20 botanical families, useful both in preventive actions and in the treatment of neoplastic diseases has been established, and polyphenolic compounds have been identified as key to the health potential of endemic diseases and desert plants. It has been shown that people who follow a diet rich in polyphenols are less prone to the risk of many cancers and chronic diseases, such as obesity and diabetes. In view of the increasing antioxidant potential of these plant species, as well as the increasing trade in herbal products from the Sahara region, phytosanitary and pharmaceutical regulations must change in this respect and should be in line with Trade Related Aspects of Intellectual Property Rights (TRIPS), and the sustainable use and development of plant products must be addressed at the same time.