Sri Lanka, together with the Western Ghats of India, constitutes one of the world’s biodiversity hotspots, renowned for its extraordinary floristic diversity and high levels of endemism. Among its biological wealth, medicinal plants hold exceptional ethnobotanical, cultural, and therapeutic significance. A considerable proportion of these species are endemic, highlighting the ecological uniqueness and global importance. However, this invaluable resource base is increasingly challenged by habitat degradation, overharvesting, invasive species, climate change, and socio-economic pressures. This chapter provides a comprehensive assessment of the taxonomic richness, distribution patterns, and ethnobotanical relevance of Sri Lanka’s endemic medicinal flora, while critically examining the threats jeopardizing their persistence. Strategies for conservation and sustainable utilization are discussed, spanning both in-situ and ex-situ approaches, such as protected areas, community-based initiatives, agroforestry cultivation, seed banks, and specialized nurseries. Additionally, the chapter emphasizes the transformative potential of advanced technologies, including tissue culture, cryopreservation, digital herbaria, Geographic Information System-based mapping, and artificial intelligence in strengthening conservation and research capacity. By integrating traditional knowledge systems with modern scientific innovations, the chapter advances a multidimensional framework for safeguarding Sri Lanka’s endemic medicinal plant diversity. Such an approach not only addresses urgent conservation priorities but also ensures the sustainable use of these irreplaceable resources for future generations.