Four cities in southern Morocco, namely Es-Smara, Laayoune, Boujdour and Dakhla, have been targeted by the ethnobotanical study of medicinal plants used in the traditional pharmacopoeia of the local population in order to highlight popular knowledge and know-how and to establish a catalog of the medicinal plants used and their therapeutic uses. The results showed that medicinal plants are used by people of both sexes belonging to different age groups and socio-economic and intellectual levels. The leaves are the most used parts and the decoction constitutes the essential preparation of the vegetable drugs in the traditional herbal medicine. In addition, digestive pathologies are the major therapeutic indications for the use of medicinal plants. The most families represented in the medicinal flora used in the studied regions of the Moroccan Sahara are Lamiaceae, Asteraceae, Chenopodiaceae, Convolvulaceae, Apiaceae and Liliaceae. The results of this ethnobotanical study could be an important source of information and a database for further research in the fields of phytochemistry and pharmacology in order to find new bioactive molecules.