Abstract: In this study, the ethyl acetate fraction of Myristica fragrans Houtt. was investigated for its in vitro anticholinesterase activity as well as neuroprotectivity against H₂O₂-induced cell death in PC12 neuronal cells and the ability to chelate bio-metals (Zn²⁺, Fe²⁺, and Cu²⁺). The fraction was inactive toward acetylcholinesterase (AChE); however, it inhibited the butyrylcholinesterase (BChE) with IC₅₀ value of 68.16 µg/mL, compared with donepezil as the reference drug (IC₅₀ = 1.97 µg/mL) via Ellman’s method. It also showed good percentage of neuroprotection (86.28% at 100 µg/mL) against H₂O₂-induced neurotoxicity and moderate metal chelating ability toward Zn²⁺, Fe²⁺, and Cu²⁺. The phytochemical study led to isolation and identification of malabaricone A (1), malabaricone C (2), 4-(4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzene-1,2-diol (3), nectandrin B (4), macelignan (5), and 4-(4-(benzo[d][1,3]dioxol-5-yl)-1-methoxy-2,3-dimethylbutyl)-2-methoxyphenol (6) which were assayed for their cholinesterase (ChE) inhibitory activity. Compounds 1 and 3 were not previously reported for M. fragrans. Among isolated compounds, compound 2 showed the best activity toward both AChE and BChE with IC₅₀ values of 25.02 and 22.36 μM, respectively, compared with donepezil (0.07 and 4.73 μM, respectively).