In vitro studies on cholinesterase inhibitory potential on the three sets of 2,3-dihydro-1,5-benzothiazepines have been carried out. The compounds in Set 1 were unsubstituted on ring A, while those in Sets 2 and 3 had a 20 - and 30 -hydoxy substituent, respectively, in ring A. These studies revealed that they are mixed inhibitors of both AChE and BChE as reflected from their IC50 values. It was further observed that 30 -hydroxy substituted benzothiazepines (Set 3) were found to have stronger affinity for both AChE and BChE compared with those of Sets 1 and 2. Moreover, all the compounds in Set 3 were found to be stronger BChE inhibitors than AChE. These experimental observations were rationalized by conducting in silico studies using molecular docking tool of Molecular Operating Environment (MOE) software, thereby, a good correlation was observed between IC50 values and their binding interactions within the enzyme active site. We have observed that these interactions were electrostatic and hydrophobic in nature besides hydrogen bonding. The high BChE inhibitory potential of 30 -hydroxy substituted benzothiazepines was found to be cumulative effect of hydrogen bonding and p–p interactions between the ligand and BChE. These findings may serve as a guideline for synthesizing more potent ChE inhibitors for the treatment of Alzheimer's disease and related dementias.