Lichens are a large group of valuable lower plants with unique features and diverse applications worldwide such as in medicine, cosmetics, food, and textile industries. They are also well known for their potential in observing climate and environmental monitoring. Their successful exploitations require reliable analytical methods to check and maintain quality and efficacy of the products based on them. This study focuses on the development of a sensitive and reliable quantification method for the analysis of important depsides, depsidones, dibenzofuran and monocyclic phenols inseven known and an unidentified lichen species. Multiple Reaction Monitoring (MRM) approach using UHPLC-QqQ-MS instrument was employed for the development of the quantitative method. Both LC and MS parameters were optimized to ensure maximum separation. High sensitivity, and selectivity. LODs and LOQs were found to be in the range of 2.1–71.5 ng/mL and 6.3–212.9 ng/mL, respectively. The accuracy (% bias) and precision (% RSD) were found to be <5% in most cases. Metabolites 1–9 were found in the range of 0.5–41429 μg/g in the analysed lichen extracts. The analysis revealed that metabolites 1, 2 and 3 are the predominant ones. This method can be used for the identification and absolute quantification of secondary metabolites in lichen extracts, and herbal or consumer products based upon them.