Fourteen sesquiterpenoids were isolated from the fruits of Alpinia oxyphylla Miq. Their structures were elucidated based on NMR analyses (1H, 13C, DEPT, 1H,1H‐COSY, HMQC, HMBC, and NOESY) and identified as 12‐nornootkaton‐6‐en‐11‐one (3), (+)‐(3S,4aS,5R)‐2,3,4,4a,5,6‐hexahydro‐3‐isopropenyl‐4a,5‐dimethyl‐1,7‐naphthoquinone (5), nootkatene (6), 9β‐hydroxynootkatone (7), 2β‐hydroxy‐δ‐cadinol (8), 4‐isopropyl‐6‐methyl‐1‐tetralone (11), oxyphyllone E (12), oxyphyllone D (13), oxyphyllanene B (15), oxyphyllone A (16), oxyphyllol E (17), (9E)‐humulene‐2,3;6,7‐diepoxide (18), mustakone (20), and pubescone (21). Among them, 3 was a new norsesquiterpenoid, 8 was a new natural product, and 5, 6, 11, 20, 21 were isolated from A. oxyphylla for the first time. Twenty sesquiterpenoids, 1–5 and 7–21, were investigated for their in vitro acetylcholinesterase (AChE) inhibitory activities, including previously isolated seven sesquiterpenoids from A. oxyphylla, (11S)‐12‐chloronootkaton‐11‐ol (1), (11R)‐12‐chloronootkaton‐11‐ol (2), nootkatone (4), oxyphyllenodiol A (9), oxyphyllenodiol B (10), 7‐epiteucrenone B (14), and alpinenone (19). TLC‐Bioautographic assay indicated that 1–4, 7, 14, 16, 18, 19, and 21 displayed anti‐AChE activities at 10 nmol. Microplate assay confirmed that 19, 18, 16, and 21 displayed moderate‐to‐weak anti‐AChE activities at the concentration of 100 μM, and 19 was the most potent inhibitor with an IC50 value of 81.6±3.5 μM. The presence of anti‐AChE sesquiterpenoids in A. oxyphylla may partially support the traditional use of this fruit for the treatment of dementia.