Constantine and Mila regions have been investigated in an ethnobotanical study for the first time. A total of 102 medicinal plants have been cited to treat human ailments. Twenty-eight new species of 31 common plants with 151 new therapeutic applications and 12 new cited species including one endemic specie Zygophyllum cornutum Coss were found as compared to other Algerian regions. In addition, to the best of our knowledge, 369 new medicinal uses of 75 known plants, were reported for the first time in the Mediterranean basin.