The Monte Carlo method was used for quantitative structure-activity relationship modeling of bis-quinolinium and bis-isoquinolinium compounds as acetylcholine esterase inhibitors for a series of 36 compounds. quantitative structure-activity relationship models were calculated with the representation of the molecular structure by the Simplified Molecular Input-Line Entry System. One split into the training and test set was examined. The statistical quality of the developed model was good. The best calculated quantitative structure-activity relationship model had following statistical parameters: r (2) = 0.8097 for the training set and r (2) = 0.9372 for the test set. Structural indicators defined as molecular fragments responsible for increases and decreases in the inhibition activity were calculated. The computer-aided design of new compounds as potential acetylcholine esterase inhibitors with the application of defined structural alerts was presented.