Glycogen synthase kinase-3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder characterized by Aβ aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function, promoting tau phosphorylation, regulating amyloid precursor protein (APP) cleavage, and triggering neuroinflammation and oxidative damage. Preclinical research highlights the potential of inhibiting GSK3 activity as a primary therapeutic approach for AD. However, pending issues include the lack of highly specific and affinity-driven GSK3 inhibitors, which need to be addressed in future research. In conclusion, GSK3 represents a promising target for AD treatment, filled with hope, challenges, opportunities, and obstacles.Glycogen synthase kinase-3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder characterized by Aβ aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function, promoting tau phosphorylation, regulating amyloid precursor protein (APP) cleavage, and triggering neuroinflammation and oxidative damage. Preclinical research highlights the potential of inhibiting GSK3 activity as a primary therapeutic approach for AD. However, pending issues include the lack of highly specific and affinity-driven GSK3 inhibitors, which need to be addressed in future research. In conclusion, GSK3 represents a promising target for AD treatment, filled with hope, challenges, opportunities, and obstacles.