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Traditional medicine uses and knowledge is more famous and well documented in rural/remote areas in Pakistan and worldwide than the urban areas. The present effort was made to document the ethnomedicinal practices among the communities of Karachi city and provides the basis for the development of natural drug discovery. We are aware of no other quantitative ethnobotanical investigation on the use of medicinal plants in the study area prior to this study. For ethnobotanical data collection, 177 local informants and traditional healers were interviewed, using semi-structured interviews.Various quantitative indices such as relative frequency of citation (RFC), fidelity level(FL), use value(UV), and the Jaccard Index (JI) were applied to the documented data. The traditional medical uses of 97 plants species belonging to 47 families were reported. Solanaceae (seven taxa) followed by Boraginaceae and Fabaceae (six taxa each), Cucurbitaceae (five taxa); Amaranthaceae, Convolvulaceae, Malvaceae, Verbenaceae and Zygophyllaceae (four taxa each) were the leading families contributed with the highest number of taxa. The highest plant-used part was leaf, with 45 reports (28.84%), followed by fruit (15.38%). It was observed that the majority of species were used to treat stomach problems, respiratory issues, general wellness, skin conditions, liver-related conditions, and fever respectively. The ethnomedical findings reported in this study offer concrete proof of the Karachi city residents' use of therapeutic plants. The research also showed that the region's medicinal plants constitute a significant source of herbal medicines used to treat ailments. This survey can serve as a starting point for future scientific research to create new plant-based pharmaceuticals for the market.