Lichens, symbiotic associations of fungi and photosynthetic algae, are rich sources of bioactive compounds with significant ecological functions and considerable pharmacological potential. This review provides an integrated overview of the morphological, ethnobotanical, structural and functional diversity of lichen metabolites. Most lichen species produce structurally diverse secondary metabolites with antimicrobial, anticancer, antioxidant, anti-inflammatory and enzyme-inhibitory effects. Despite centuries of traditional use, challenges persist in isolating individual metabolites because of their complex thallus structure, low solubility and sensitivity to conventional extraction methods. However, modern advancements, including axenic cultivation, genome mining, molecular networking and next-generation analytical technologies, have enabled the discovery of previously undetectable metabolites and provided deeper insights into their biosynthetic pathways. Advancing lichen research by combining traditional knowledge with modern biotechnological innovations will be pivotal for identifying new, sustainable therapeutic molecules that meet emerging global healthcare demands.