Novel anti-butyrylcholinesterase inhibitors containing, oxadiazole derivatives, were designed and these molecules were subjected to molecular docking study. The docking study revealed that the designed compounds possess significant to moderate interaction with the targeted enzyme butyrylcholinesterase. Among them compound 3 (10.8k/cal) and 52 (10.4 k/cal) showed similar docking compared to donepezil (12.76 K/cal). Remaining compound shows good to moderate activity compared to standard drug. The target compounds were evaluated for their inhibitory activity against the BuChE. Among these new derivatives, 3 (71.02±4.3nM) was found to inhibit cholinesterase catalyticdomain most significantly, and then compound 52 (72.37±4.3nM) possessed significant cholinesterase. Compound 3 and 51 have more inhibitory activity than the remaining tested compounds.This may be due to the presence of more electronegative atoms (OCH3) in thesubstitution. The remaining tested compoundshave moderate to good inhibitory activity against the BuChE. In addition, ADMET prediction results indicated that these compounds might be less toxic and display more interesting pharmacokinetic properties.