Schiff bases gaining remarkable importance day by day in the current situation Schiff bases are found to be a valuable pharmacophore for the synthesis and development of various biologically active heterocyclic compounds. In recent past, we have reported various classes of compounds as enzyme inhibitors, in continuation; A series of 2-Mercaptobenzimidazole hydrazone derivatives (9-42) were synthesized through multistep reactions in high yields and evaluated for butyrylcholinesterase inhibition. In present study, 2-ethylthio benzimidazole was formed by the reaction of 2-Mercaptobenzimidazole with bromoethane. In the second step (2-(2-(ethylthio)benzimidazolyl)acetate) obtained by the reaction of 2-ethylthio benzimidazole with ethyl chloroacetate. In the third step, 2-(2-(ethylthio)benzimidazolyl)acetate was refluxed in methanol with hydrazine hydrate and get 2-((ethylthio)benzimidazolyl)acetohyrazide. In the last step, 2-((ethylthio)benzimidazolyl)acetohyrazide was reacted with different aldehydes in the presence of glacial acetic acid (catalyst) to get a series of 2-Mercaptobenzimidazole hydrazone derivatives. Product was characterized by 1H NMR and 13C NMR. These newly synthesized compounds showed varying degree of butyrylcholinesterase inhibition. Compound no. 15 with (IC50 = 25.10 and#177; 0.90 and#181;M) was found to be most active in the whole series. Similarly, compounds 42, 12, 40, 17, 22, 28 and 09 exhibited excellent activity with IC50 values are (IC50 = 25.36 and#177; 0.57 and#181;M, IC50 = 27.30 and#177; 0.52 and#181;M, IC50 = 34.31 and#177; 0.59 and#181;M, IC50 = 51.29 and#177; 0.64 and#181;M, IC50 = 54.52 and#177; 0.95 and#181;M, IC50 = 57.90 and#177; 0.45 and#181;M and IC50 = 60.93 and#177;0.67 and#181;M) respectively as compared to standard galantamine 18.13and#177;0.20 and#181;M. Molecular docking helped to find interactions between butyrylcholinesterase enzyme and test compounds. This study results that Schiff bases have been discovered a new class of butyrylcholinesterase inhibitors which have not been discovered earlier.