The extensive disposition of amyloid-beta (Ab) plaques cemented between the nerve cells have been known to hold decisive clues to an age-related neurodegenerative disorder – Alzheimer’s disease (AD), which is the most prevalent cause of dementia among older people over 65. The progressive memory deficits and other disturbances in Alzheimer’s patients’ daily activities have often been observed and associated with significant social burden, eventually leading to the increase of morbidity and mortality. Because of the modest therapeutic benefit seen with currently available cholinesterase inhibitors and NMDA-receptor antagonist, it is critical to develop novel treatment options for AD. In this regard, our study aims to design, synthesize, and evaluate phenylthiazole based compound libraries with anti-Ab activity as disease-modifying agents in treating AD. A library of these novel small molecules was synthesized and evaluated for their anti-amyloid aggregation activity in the presence and absence of Ab using the thioflavin T (ThT)-based fluorescence spectroscopy. The binding interactions were investigated by the computational studies. These investigations have shown that phenylthiazole based derivatives are capable of preventing Abaggregation. Future studies such as transmission electron microscopy (TEM) experiments, and the in vitro cell-based assays and in vivo studies will provide more insight on the potential of these novel compounds to treat AD.