Biodiversity hotspots, harbouring a significant proportion of the world’s endemic species, are repositories of immense medicinal plant wealth. Medicinal plants are of utmost importance in both traditional and modern pharmacotherapies, serving as primary sources of bioactive compounds in the development of drugs. However, accelerating global climate change poses serious threats to their survival, genetic variability, and phytochemical stability. Changes in temperature regimes, precipitation patterns, and the increasing frequency of extreme climatic events are reshaping habitats, disrupting reproductive biology and interactions with pollinators, and resulting in fragmented populations and genetic erosion. Simultaneously, climate-induced abiotic stress alters metabolic pathways, leading to qualitative and quantitative changes in major secondary metabolites, thereby affecting the medicinal potency and safety. This chapter highlights the ecological and genetic responses of medicinal plants to climate stress, phytochemical profile alterations, and changes in therapeutic attributes, based on evidence derived from biodiversity hotspots around the world, such as the Himalayas, the Amazon Basin, and the Mediterranean region. Updated conservation approaches discussed in this chapter include classical and molecular tools, metabolomics, ecological modelling, and community-based strategies for the preservation of medicinal plant resources. The chapter provides critical insights into emerging challenges and future perspectives for protecting the genetic and phytochemical diversity of medicinal plants under the changing climatic regimes.