The identification of novel drugs for neurodegenerative diseases such as Alzheimer’s and Parkinson’s are complex as they are associated with more than one distinct cause and multiple disease mechanisms with multiple drug targets. For Alzheimer’s disease (AD), despite extensive research, there are currently no drugs available that can improve clinical symptoms permanently and with moderate efficacy. Numerous target-specific chemical or biologic drugs, proposed earlier, were either abandoned due to their limited potency to a single mechanistic target enzyme or failed in clinical trials due to adverse side-effects and impaired blood--brain barrier efficacy. At this outset, finding an efficient multi-target drugs with adequate bioavailability and drug likeliness against this AD is essential. This work focuses on an in-house strategically designed database of quinazolinone derivatives and performed a detailed ADMET screening to explore the pharmacokinetic actions of the molecules. A select set of lead molecules were further probed into their sequential molecular docking towards the simultaneous inhibition of three therapeutic targets of AD (acetylcholinesterase, butyrylcholinesterase, and β-secretase). The effort has successfully identified few novel inhibitors of AD pathogenesis with ‘multi-targeted potency’. This finding opens the door for further research into these lead compounds as potential therapeutics for the efficient triple inhibition of three crucial enzymes of amyloid-based and cholinergic mechanisms for AD pathogenesis. The report additionally unlocks an innovative ‘One Drug-Multiple Target’ ligand construction approach to deal with the complicated multifunctional nature of AD.