Pilocarpus microphyllus Stapf. ex Wardlew. (Rutaceae) is an endemic and threatened medicinal plant species from tropical Brazil. Popularly known as “jaborandi”, it is the unique natural source of pilocarpine, an alkaloid used to medical treat glaucoma and xerostomia. Based on Species Distribution Models (SDMs), we modeled the suitability of P. microphyllus’s geographical distribution considering three Global Circulation Models (GCMs) under two future climate change scenarios (SSP2-4.5 and SSP5-8.5). The quantitative analyses carried out using ten different SDM algorithms revealed that precipitation seasonality (Bio15) and precipitation of the driest month (Bio14) were the most important bioclimatic variables. The results evidenced four main key areas of continuous occurrence of the plant spreading diagonally over tropical Brazilian biomes (Amazon, Cerrado and Caatinga). The near-future (2020 to 2040) ensemble projections considering all GCMs and scenarios have indicated negative impacts for the potential loss or significant reduction in suitable habitats for P. microphyllus in the transition region between the Amazon and Cerrado into central and northern Maranhão state, and mainly in the Caatinga biome over the northern Piaui state. On the other hand, positive impacts of the expansion of the plant habitat suitability are projected over forest cover protected areas of the Amazon biome in the southeastern Pará state. Since the jaborandi is of socioeconomic importance for many families in the north/northeast Brazil, it is urgent to implement public policies for conservation and sustainable management, thus mitigating the impacts of global climate change.