Natural products have been considered as safer acetylcholinesterase inhibitors (AChEIs) for Alzheimer’s disease treatment. ZINC000038661945, ZINC000002104243, and ZINC000071318273 are natural products reported to have potency as AChEIs. This study aimed to identify the interactions and stability of ZINC000038661945, ZINC000002104243, and ZINC000071318273 in the AChE active site. The methods used were 100 molecular docking and 15-ns molecular dynamics (MD) simulations using YASARA-Structure. The RMSD values of native ligand redocking were ≤ 2.000 Å, indicating the molecular docking protocol was valid. Molecular docking resulted in 1 cluster of best-docked of ZINC000038661945 and ZINC000002104243 whilst 2 clusters of best-docked ZINC000071318273. ZINC000038661945, ZINC000002104243, and ZINC000071318273 showed stable interactions with amino acid residues in the AChE active site during MD simulations with ΔRMSD-Backbone and ΔRMSD-LigMove ≤ 2.000 Å in the last 5 ns of the simulations. The interactions that were formed included hydrogen, aromatic, and hydrophobic interactions. The average binding energy of first cluster of all ZINC respectively were 9.508 ± 0.414 kJ/mol, 9.344 ± 0.427 kJ/mol, and 6.531 ± 0.382 kJ/mol where the second cluster of ZINC000071318273-AChE was 6.777 ± 0.359 kJ/mol. ZINC000038661945 dominantly interacted with Tyr334, whilst ZINC000002104243 dominantly interacted with Trp84 and Phe330. ZINC000071318273 showed dominant interaction with Tyr334, Phe330, and Phe331.