Alzheimer's disease (AD) stands as a formidable neurodegenerative ailment that poses a substantial threat to the elderly population, with no known curative or disease-slowing drugs in existence. Among the vital and time-consuming stages in the drug discovery process, disease modeling and target identification hold particular significance. Disease modeling allows for a deeper comprehension of disease progression mechanisms and potential therapeutic avenues. On the other hand, target identification serves as the foundational step in drug development, exerting a profound influence on all subsequent phases and ultimately determining the success rate of drug development endeavors. Machine learning (ML) techniques have ushered in transformative breakthroughs in the realm of target discovery. Leveraging the strengths of large dataset analysis, multifaceted data processing, and the exploration of intricate biological mechanisms, ML has become instrumental in the quest for effective AD treatments. In this comprehensive review, we offer an account of how ML methodologies are being deployed in the pursuit of drug discovery for AD. Furthermore, we provide an overview of the utilization of ML in uncovering potential intervention strategies and prospective therapeutic targets for AD. Finally, we discuss the principal challenges and limitations currently faced by these approaches. We also explore the avenues for future research that hold promise in addressing these challenges.Copyright © 2023 Elsevier B.V. All rights reserved.