Triazole and triazoles fused with six-membered ring systems are found to possess diverse applications in the field of medicine, agriculture and industry. The 1,2,4-triazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines derivatives were synthesized as cholinesterase inhibitors. The reaction of 1H-indol-3-acetic acid with thiocarbohydrazide gave the 4-amino- 3-mercapto-5-[(1H-indol-3-yl)methyl]-4H-1,2,4-triazole. The reaction of triazole with arylaldehydes in ethanol gave the 4-arylideneamino-3-mercapto-5-[(1H-indol-3-yl)methyl]-4H- 1,2,4-triazoles. The 3-[(1H-indol-3-yl)methyl]-6-aryl-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines were obtained by condensing triazole with phenacylbromides in absolute ethanol. The chemical structures of the compounds were elucidated by IR, 1H-NMR and FAB+-MS spectral data and elemental analysis. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman's spectrophotometric method. Compounds 1b and 1c can be identified as promising anticholinesterase agents due to their inhibitory effect on AChE with IC50 value of 96.45±8.14 and 76.24±6.42 μM respectively when compared with Donepezil (IC50 =0.056±0.001μM).