Abstract Knowledge of Manabians about medicinal plants use contributes to filling gaps of information on natural and traditional medicine in Ecuador. This descriptive research had the objective of deepening the uses knowledge of medicinal plants in Membrillal, Julcuy, Pedro Pablo Gómez and Quimis, Southern Manabi. The data were provided by 200 interviewees from July to November 2019. In addition to the sociocultural interview component (age, gender, educational level), the interview also included information about knowledge of the medicinal plants, plant parts, use, the forms of use, frequency of use, purposes of use, the abundance in the region, the environment surrounding the plant, distance from home to plant collection, and time of collection. The phytochemical characteristics of the plant was also studied, which validated the medicinal use. In total 144 plant species with some medicinal use were identified by the interviewees. The plant species identified belonged to 58 botanical families and 118 genus. The most frequently identified families were Fabaceae, Lamiaceae, Asteraceae and Rutaceae. The species Mentha spicata L. and Cymbopogon citratus (DC.) Stapf, were the most frequently described. The plant parts most frequently used were leaves (65.5 % of interviewees) to make infusions (70.5 % of interviewees). Digestive system diseases as well as infectious and parasitic diseases were the mostly treated diseases with the medicinal plants, with a interviewee frequency of 35.9 %, 27.8 %, 30.3 % and 35.0 % in Membrillal, Julcuy, Pedro Pablo Gomez and Quimis, respectively. The bioactive principles of the medicinal plants described by the interviewees were flavonoids, phenols, triterpenoids and alkaloids.