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Three new oxygenated xanthones, fuscaxanthones L-N (1-3), and 14 known xanthones 4-17, together with the other known metabolites 18-20 were isolated from the stem barks of Garcinia fusca Pierre. Their chemical structures were determined based on NMR and MS spectroscopic data analysis, as well as single X-ray crystallography. The geranylated compounds, cowanin (13), cowagarcinone E (15), norcowanin (16) and cowanol (17) exhibited potent inhibitions against acetylcholinesterase (AChE) (IC 50 0.33-1.09 μM) and butyrylcholinesterase (BChE) (IC 50 0.048-1.84 μM), which were more active than the reference drug, galanthamine. Compound 15 was highly potent BChE inhibitor (IC 50 0.048 μM) and was 76-fold more potent than the drug. Structure-activity relationship studies indicated that the C-2 prenyl and C-8 geranyl substituents in the tetraoxygenated scaffold are important for high activity. Molecular docking studies revealed that the leads 13 and 15-17 showed similar binding orientations on both enzymes and very well-fitted at the double binding active sites of PAS and CAS with strong hydrophobic interactions from both isoprenyl side chains., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)