Increased resistance and side effects of synthetic pharmaceutical drugs have led to the exploration of bioactive compounds from alternative sources. Therefore, research on drug development from members of natural sources has gained much importance. Lichens are a unique association of fungi and algae, producing a wide array of secondary metabolites which has immense pharmacological activities. Lichen extracts have been used in traditional systems of medicines and are known to cure several diseases. Parmotrema is a large genus of foliose lichen belonging to the family Parmeliaceae. Parmeloid lichens are a diverse and ubiquitous group of lichens. Members of the Parmeliaceae family have been used in several traditional systems of medicines. One hundred and nine articles have been reported till date regarding pharmacological activities of Parmotrema species. Studies reveal that Parmotrema exhibits numerous biological activities ranging from anti-microbial, anti-fungal, anti-oxidative, and anti-proliferative properties. These properties can be attributed to the presence of pharmacologically active compounds like depsides, depsidones, phenolics, polysaccharides, lipids, diphenyl ethers, and dibenzofurans. The free radical scavenging activity and cytotoxicity specifically towards cancer cells infer that this lichen genus can have potential anti-cancer properties and should be extensively investigated for pharmaceutical purposes. This review dealt with the in-depth potentiality of this novel lichen Parmotrema species and its role in pharmacology. © 2021 Har Krishan Bhalla & Sons.