Looking for an effective anti-Alzheimer's agent is very challenging; however, a multifunctional ligand strategy may be a promising solution for the treatment of this complex disease. We herein present the design, synthesis and biological evaluation of novel hydroxyethylamine derivatives displaying unique, multiple properties that have not been previously reported. The original mechanism of action combines inhibitory activity against disease-modifying targets: β-secretase enzyme (BACE1) and amyloid β (Aβ) aggregation, along with an effect on targets associated with symptom relief - inhibition of butyrylcholinesterase (BuChE) and γ-aminobutyric acid transporters (GATs). Among the obtained molecules, compound 36 exhibited the most balanced and broad activity profile (eeAChE IC<sub>50</sub> = 2.86 μM; eqBuChE IC<sub>50</sub> = 60 nM; hBuChE IC<sub>50</sub> = 20 nM; hBACE1 IC<sub>50</sub> = 5.9 μM; inhibition of Aβ aggregation = 57.9% at 10 μM; mGAT1 IC<sub>50</sub> = 10.96 μM; and mGAT2 IC<sub>50</sub> = 19.05 μM). Moreover, we also identified 31 as the most potent mGAT4 and hGAT3 inhibitor (IC<sub>50</sub> = 5.01 μM and IC<sub>50</sub> = 2.95 μM, respectively), with high selectivity over other subtypes. Compounds 36 and 31 represent new anti-Alzheimer agents that can ameliorate cognitive decline and modify the progress of disease.