Abstract: This study aimed to investigate inhibitory effects of methanolic root extract of Xylocarpus moluccensis against cyclooxygenase, 5-lipoxygenase and acetyl cholinesterase enzymes using in vitro models. Based on bioassay guided, the extract yielded two fractions A and B. The fractions were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The major component of fraction A was identified to be α-guaiene (98.54%). For fraction B (oil), 15 components were identified. The α-guaiene fraction showed strong activities against, AchE (IC50 21 μgmL–1), 5-lipox (IC50 27 μgmL–1) and COX-1 (IC50 43 μgmL–1). It was weaker against COX-2 with IC50 of 84 μgmL–1. The oil possessed strong activities against 5-lipox and AchE with IC50 of 33 and 25 μgmL–1, respectively. However, it was weaker against both the COX enzymes (IC50 values ≥125 μgmL–1). Indomethacin, zileuton and galanthamine were used as positive controls. Concentration responses of the α-guaiene and oil against the enzymes were obtained using 5 concentrations (25-125 μgmL–1). Means were plotted in a graph with error bars representing 95% confidence intervals. For the α-guaiene, the inhibition response increased significantly with the increase of concentrations from 25-100 μgmL–1 against the four tested enzymes. Both the isolates showed remarkable dual inhibitory effects against 5-lipox and AchE enzymes. The results indicated the potential therapeutic effects of the plant in the treatment of inflammatory related ailments and cognitive disorders. Further study is needed to verify mechanism of actions and effective doses. The isolation and the biological activities observed contribute to the novelty of this study.