Benzimidazole-based pyrrole/piperidine analogs (1–26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1–13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC₅₀ = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC₅₀ = 16.11 ± 0.33 µM) and galantamine (IC₅₀ = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC₅₀ values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC₅₀ = 18.14 ± 0.05 µM) and galantamine (IC₅₀ = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14–26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC₅₀ = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC₅₀ = 20.01 ± 0.12 µM) and galantamine (IC₅₀ = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC₅₀ values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC₅₀ = 18.14 ± 0.05 µM) and galantamine (IC₅₀ = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of −10.50, −9.3, −7.73 and −7.8 for AChE and −8.97, −8.2, −8.20 and −7.6 for BuChE, respectively.