INTRODUCTION:Pseudevernia furfuracea, a lichen used classically for cosmetic applications, contains interesting metabolites possessing antimicrobial and anti-inflammatory or antioxidant properties. OBJECTIVES:Ionic liquid combined to microwave-assisted extraction (IL-MAE) was successfully applied for metabolites extraction from Pseudevernia furfuracea. MATERIALS AND METHODS:Three imidazolium and pyridinium-based ionic liquids (ILs): 1,3-dimethylimidazolium methylsulphate [C1 C1 Im][MeSO4 ], 1-ethyl-3-methylimidazolium ethylsulphate [C2 C1 Im][EtSO4 ], and N-ethylpyridinium ethylsulphate [C2 Py][EtSO4 ] were assessed for this process. The efficiency of the extraction method was evaluated using thin-layer chromatography (TLC) coupled to a Camag® spectrophotodensitometer and using high-performance liquid chromatography (HPLC) analysis. RESULTS:ILs under MAE showed extraction time efficiency (15 min vs. 24 h for conventional heating) and high selectivity in extracting the targeted metabolites: atranorin (AT), methyl-β-orcinol carboxylate (MOC), fumarprotocetraric acid (Fum. Ac.), and physodic acid (Phys. Ac.) despite the increased degradation of AT under MAE. We showed a tunable selectivity of ILs towards extracting metabolites by changing anion or cation due to the modification of the interaction between the IL and the metabolites. While [C2 Py][EtSO4 ] was the most efficient IL and could extract all the targeted metabolites, [C2 C1 Im][EtSO4 ] was the most selective. It fully extracted AT and partially Fum. Ac. Moreover, the lichen prepared by mixing procedure provided AT and Fum. Ac. more than the milled one. A 100 times scale-up extraction was successfully performed on mixed samples with full IL recycling after back extraction. CONCLUSION:IL-MAE is reliable for lichen metabolites extraction. The method is reproducible, scalable, with possible IL recycling, opening the door for potential industrial applications.