Sleep deprivation (SD) is a significant contributor to neuroinflammation, oxidative stress, and cognitive dysfunction, with its mechanisms closely linked to astrocyte activation. As key regulators of the central nervous system, astrocytes exhibit dual roles in SD through A1/A2 polarized phenotypes: A1 astrocytes exacerbate neuroinflammation and synaptic damage by releasing pro-inflammatory factors and neurotoxins, whereas A2 astrocytes promote neural repair via secretion of neurotrophic factors and anti-inflammatory mediators. This review systematically summarizes the activation mechanisms of astrocytes in SD and related signaling pathways, including NF-κB, MAPK, SHH and JAK-STAT. Chronic SD induces cognitive impairment through the accumulation of inflammatory mediators and hyperactivation of astrocytes, while modulating their polarization phenotypes (e.g., suppressing A1 or enhancing A2) may serve as novel strategies for intervening in SD-related neural injuries. Future studies should further elucidate the spatiotemporal specificity of astrocyte polarization and interactions within signaling networks to provide a theoretical basis for targeted therapies.