This project is confined to first report on comprehensive ethnobotanical exploration of medicinal plants in deserts of Sindh. The study is based on ethnopharmacological exploration of traditional knowledge regarding the medicinal uses of plants in selected areas of deserts Sindh that are Tharparkar, Badin, Umerkot, Mirpurkhas, Sanghar and Khairpur. Classical to applied ethnobotanical approaches were applied to document the ethnomedicinal data and their analysis using relative importance (RI), Use value (UV), relative frequency of citation (RFC), fidelity level (FL), informant consensus factor (ICF) and disease consensus index (DCI). In total, various number of informants including 186 (Tharparkar and Badin), 174 (Sanghar and Khairpur), 155 (Umerkot and Mirpurkhas) and 157 (for diabetes) were interviewed using ethnobotanical methods. In addition to this, 161 medicinal plant species belonging to 42 families were reported by ethnic communities and reported species collected for preservation of Herbarium specimen to be submitted to Herbarium as reference specimens. The most dominant life form was herbs (105 species) while most predominantly reported families were Fabaceae (20 species), Amaranthaceae (14 species), and Cucurbitaceae (13 species). The most prevalent diseases belonged to gastrointestinal, respiratory and reproductive disorders. It is reported in this project that the most used common methods of herbal drug preparations were powder and decoctions in all regions of study area. The most commonly known species on the base of RFC, UV and RI in various study regions were Citrullus colocynthis, Citrullus lanatus, Boerhavia procumbens, Cressa cretica (Tharparkar and Badin), Ziziphus jujuba, Sesamum indicum, (Sanghar and Khaipur), Oxalis corniculata, Amaranthus viridis, Ocimum tenuiflorum (Umerkot and Mirpurkhas) and Azadirachta indica (for diabetes). On the base of FL, 13 species (Tharparkar and Badin), 5 species (Sanghar and Khaipur) and 16 species (Umerkot and Mirpurkhas) were found to be important in treating specific diseases with maximum FL values (100%). In treated disease categories, high ICF was reported for gastrointestinal disorders in Tharparkar, Badin, Sanghar and Khairpur whereas in Umerkot and Mirpurkhas, maximum ICF was reported for disorders of sensory organs. For treatment of diabetes, high DCI was reported for Ocimum gratissimum, Calotropis procera and Taraxacum officinale. It is concluded that folklore medicine in rural communities of deserts of Sindh is an important source of primary healthcare. XX The traditional knowledge of plants shown in relation to medicinal use, reflecting a striking diversity of species and uses, as well as their importance in plant-based therapies in deserts of Sindh. Data regarding ethnomedicinal uses indicate a high degree of plant knowledge still exist among ethnic communities for treating commonly occurring diseases. Moreover, the importance of traditional medicines and indigenous knowledge may contribute to the development of the management, conservation and sustainable use of medicinal flora in deserts in Sindh. The present study constitutes a good basis for further phytochemical and pharmacological research, which could be of interest in the design of new drugs. Furthermore, the evidence of these folk uses coupled with high ethnobotanical indices including RFC, UV, RI, FL and DCI could be the key information for future phytochemical and pharmacological studies and thereby give rise to new medicinal resources. In addition, species with only a few documented traditional uses may be further explored for preservation of traditional knowledge to them.