Several isoquinoline alkaloids (1-18), which have basic chemical structures as protoberberine and aporphine skeletones, were evaluated for their inhibitory activities on AChE and BuChE. Among them, compounds 3, 4, 6, 8 and 12 showed the potent AchE activity with the IC50 values ranging from 10.2±0.5 μM to 24.5±1.6 μM, meanwhile, compound 14-17 exhibited strong inhibitory activity with IC50 values from 2.1±0.2 to 5.5±0.3 μM. Compounds 14-17 exhibited selective inhibition for AChE compared with BuChE. The isoquinoline alkaloid possesses aromatic methylenedioxy groups and quaternary nitrogen atoms are crucial for the anti-cholinesterase inhibitory activity.