These findings show that pipericine (C2) has a greater inhibition efficiency toward AChE than the other compounds due to its favorable bonding of hydrophobic–hydrophilic interactions, acceptable binding geometry, and satisfactory occupation of both the CAS and PAS binding sites, which suggests that pipericine is a potential natural AChE inhibitor for the treatment of neurodegenerative disease and Alzheimer’s disease. Here, ACHE is linked to neurodegenerative disease.