Alzheimer’s disease (AD) has become a significant public health problem, but the therapeutic options are limited. Recently, ADUHELM® (Biogen) was conditionally approved as a new AD drug targeting pathogenic amyloid beta in the patient’s brain. However, there is still an urgent need for affordable and more effective AD drugs. Therefore, we aim to accelerate AD drug discovery using our three-dimensional Alzheimer’s in a Dish™ (ADiD) model as a drug screening platform. In this ongoing project, we will identify and validate novel AD drug candidates from libraries of natural products and FDA-approved drugs that reduce pathogenic amyloid beta accumulation and/or amyloid-induced synaptic/neuronal deficits. In addition, we will test and validate AD resilience-enhancing drug candidates that are predicted from bioinformatic analysis. Our study’s overarching goal is to find novel drug candidates that can reduce pathogenic amyloid beta oligomers/aggregates and their toxicity, and that are clinically applicable and affordable for most AD patients.