The potential of endemic medicinal plants in Yemen for sustainable pharmaceutical applications is home to a diverse and unique flora, with a significant proportion of endemic and near-endemic species that are traditionally used in folk medicine. This study documents 16 medicinal plant species from Abyan Governorate, Southeastern Yemen, and analyzes their traditional therapeutic uses and the extent to which they have been phytochemically investigated. The majority of these species are used to treat skin diseases, wounds, and burns. However, the findings indicate that 56.3% of these plants have not yet been studied for their active compounds. The Asclepiadaceae family was the most represented among the studied taxa, yet remains largely chemically unexplored. The study emphasizes the importance of preserving ethnobotanical knowledge and recommends future phytochemical screening and pharmacological validation of under-researched species for sustainable use in pharmaceutical development.