Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no known cure, which has prompted the exploration of novel therapeutic approaches. The clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) tool has generated significant interest for its potential in AD therapeutics by correcting faulty genes. Our report comprehensively reviews emerging applications for CRISPR-Cas9 in developing in vitro and in vivo models for AD research and therapeutics. We further assess its ability to identify and validate genetic markers and potential therapeutic targets for AD. Moreover, we review the current challenges and delivery strategies for the in vivo application of CRISPR-Cas9 in AD therapeutics.