Studies on medicinal ethnobotany in rural areas and communities are important for documentation and generation of indigenous knowledge on the medicinal use of plants, as well as identification of new botanicals of pharmacological significance. This paper presents, for the first time, the quantitative ethnobotanical uses of medicinal plants in Ile-Ife, Osun State, Nigeria. The ethnobotanical survey was carried out by conducting semistructured interviews with 70 informants/collaborators. Data were analyzed using various quantitative indices, namely, Ethnobotanical Knowledge Index (EKI), Species Popularity Index (SPI), Relative Frequency of Citation (RFC), Cultural Importance Index (CII), Informant Consensus Factor (FIC), Fidelity Level (FL), and Species Therapeutic Index (STI). A total of 87 plant species belonging to 43 families were documented along with their medicinal uses. Euphorbiaceae is the most implicated family (9%) of the plants documented, and herbs (36%) were the prevalent life form while leaf (46%) was the most used plant part. Fevers are the most common diseases treated with the medicinal plants with 1012 use-reports, followed by skin diseases with 314 use-reports while the most common mode of preparation is decoction (37%). Telfaria occidentalis has the highest SPI and RFC (0.99, 0.99) while Khaya grandifoliola has the highest CII of 1.91. The community has EKI of 0.57 indicating a good knowledge of medicinal plants around them. Species such as Citrus aurantifolia, Khaya grandifoliola, and Ocimum gratissimum have high quantitative indices suggesting that they are effective in the treatment of various diseases in the community and therefore should be considered for pharmacological studies to validate their folkloric usages.