Traditional medicinal plant knowledge in Yemen is still only passed on orally from one generation to another. A few studies, mostly very limited in scope, have been dedicated to this indigenous knowledge so far. This paper presents the results of the first extensive field study in southern mainland Yemen, undertaken in three communities in the central region of Abyan governorate. The study is aimed to preserve the heritage of this indigenous knowledge and to explore and select local medicinal plants that promise high pharmacological efficacy for further pharmacological and phytochemical investigations.356 indigenous informants (273 males, 83 females) were interviewed about the modes of application and uses of the medicinal plants in the region. The ethnobotanical data were recorded by semi-structured face-to-face interviews, substantiated by specimen collections and taxonomic identifications and quantitative data analysis including informant consensus factor (ICF) and number of use-reports.In total, 195 medicinal plant species (170 wild and 25 cultivated) belonging to 138 genera and 55 flowering plant families, were recorded for the treatment of 155 different ailments classified into 16 categories. Apocynaceae (25 species), Fabaceae (18 species), Euphorbiaceae (16 species) and Asteraceae (14 species) were the most frequently used plant families. Paste (86) followed by unprepared plant exudates (77) and decoction (55) were the most common herbal preparation modes. Dermal application (51.8%) was the most common administration route. The highest number of use reports and the maximum number of used medicinal plants were recorded for treatment of skin and gastrointestinal ailments. Forty-five species have never been reported in the ethnomedicinal literature before. Plant species with the most citations were Aloe vacillans Forssk. (malaria), Solanum incanum L. (tooth decay), Caralluma awdeliana (Deflers) A. Berger (diabetes), Tribulus terrestris L. (kidney stones), Aristolochia bracteolata Lam. (snake poison), Hydnora abyssinica A.Br. (stomach ulcer), Indigofera oblongifolia Forssk. (urine retention) and Chrozophora oblongifolia (Delile) A. Juss ex Spreng (haemorrhoids).Significant traditional knowledge of the uses of local medicinal plant species was recorded for the first time for central Abyan in particular and southern Yemen in general. The study shows that the medicinal plants still play an important role in the primary health care in the study area. The ethnobotanical results provide a basis for further pharmacological, biological, pharmacognostical, and phytochemical investigations.