Abstract: Ethnobotanical studies were conducted to collect information about medicinal plants of Asclepiadaceae used in the treatments of various ailments and to identify the knowledgeable traditional healers among different communities in rural areas of Madurai district, Tamil Nadu, India. Information presented in this document was gathered from different community people involving in the traditional practices using standardized questionnaires. 25 informants including both male and female with different age groups were interviewed on the medicinal uses of local plants of Asclepiadaceae in this study area during October 2010-September 2011. A total of 27 plant species belonging to the family Asclepiadaceae have been reported to be in use among the rural people of different community of the study area. Among them Tylophora indica, Pergularia daemia, Sarcostemma acidum, Gymnema sylvestre, Hemidesmus indicus, Caralluma adscendens and Calotropis gigantia are leading species frequently used for a variety of health problems. As reported by informants, leaves are the most important part used for herbal preparations followed by whole plant, root, stem, latex, tuber and seed. The study revealed that rural people irrespective of community other than tribals do have a great faith in the traditional healing system and they rely on medicinal plants for treatment of various illnesses. Scientific investigation of many species of Asclepiadaceae may lead to invention of novel bioactive compounds to use them efficiently in phytotherapies. Moreover, standardized agro-techniques for pharmaceutically valuable species of Asclepiadaceae are yet to be developed for sustainable utilization.