As levels of acetylcholinesterase (AChE) decrease while levels of butyrylcholinesterase (BChE) increase in later stages of Alzheimer's disease (AD), BChE stands out as a promising target for treatment of AD. Therefore, several benzimidazole-carbamates were designed based on docking studies to inhibit BChE selectively over AChE, while retaining a reasonable solubility. Synthesized molecules exhibit IC<sub>50</sub> values from 2.4 μM down to 3.7 nM with an overall highly hBChE-selective profile of the designed compound class. After evaluation of potential neurotoxicity, the most promising compound was further investigated <i>in vivo</i>. Compound 11d attenuates Aβ<sub>25-35</sub>-induced learning impairments in both spontaneous alternation and passive avoidance responses at a very low dosage of 0.03 mg kg<sup>-1</sup>, proving selective BChE inhibition to lead to effective neuroprotectivity in AD.