Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive cognitive decline and the accumulation of amyloid-beta plaques, tau tangles, and neuroinflammation in the brain. Postoperative cognitive dysfunction (POCD) is a prevalent and debilitating condition characterized by cognitive decline following neuroinflammation and oxidative stress induced by procedures. POCD and AD are two conditions that share similarities in the underlying mechanisms and pathophysiology. Compared to normal aging individuals, individuals with POCD are at a higher risk for developing AD. Emerging evidence suggests that astrocytes, the most abundant glial cells in the central nervous system, play a critical role in the pathogenesis of these conditions. Comprehensive functions of astrocyte in AD has been extensively explored, but very little is known about POCD may experience late-onset AD pathogenesis. Herein, in this context, we mainly explore the multifaceted roles of astrocytes in the context of POCD, highlighting their involvement in neuroinflammation, neurotransmitter regulation, synaptic plasticity and neurotrophic support, and discuss how POCD may augment the onset of AD. Additionally, we discuss potential therapeutic strategies targeting astrocytes to mitigate or prevent POCD, which hold promise for improving the quality of life for patients undergoing surgeries and against AD in the future.Copyright © 2024 Elsevier B.V. All rights reserved.