Medicinal and Aromatic Plants (MAPs) play a critical role in providing ecosystem services through their provision of herbal remedies, food and natural skin care products, their integration into local economies, and maintaining pollinators’ diversity and populations and ecosystem functioning. Mountainous regions, such as Chelmos-Vouraikos National Park (CVNP), represent unique reservoirs of endemic MAP diversity that require conservation prioritisation. This study aims to provide insights into the sustainable management of MAPs, contributing to efforts to protect Mediterranean biodiversity amid the dual challenges of climate and land-use change, using a suite of macroecological modelling techniques. Following a Species Distribution Modelling framework, we investigated the vulnerability of endemic and non-endemic MAPs to climate and land-use changes. We examined the potential shifts in MAP diversity, distribution, and conservation hotspots within the CVNP. Our results revealed species-specific responses, with endemic taxa facing severe range contractions and non-endemic taxa initially expanding but eventually declining, particularly under land-use change scenarios. Local biodiversity hotspots are projected to shift altitudinally, with considerable area losses in the coming decades and elevated species turnover predicted throughout the CVNP, leading to biotic homogenization. Climate and land-use changes jointly threaten MAP diversity, calling for adaptive conservation strategies, thus highlighting the importance of proactive measures, such as awareness raising, establishing plant micro-reserves, assisted translocation, and promoting sustainable harvesting to protect these species within the CVNP. Our study offers vital insights for managing biodiversity hotspots amid global change pressures, stressing the need to integrate ecological and socioeconomic factors.