Astrocytes regulate brain metabolism and homeostasis, but how oxidative stress reshapes astrocytic metabolism to drive neuronal damage remains unclear. Here, we demonstrate that oxidative stress turns on astrocytic type I collagen (COL1) production via a redox-glycosylation coupling mechanism. Hydrogen peroxide (H2O2) suppresses miR-29 and enhances fucosyltransferase 8 (FUT8)-mediated core fucosylation, integrating post-transcriptional and glycosylation-dependent regulation of COL1. Astrocyte-derived COL1 activates integrin signaling and promotes neuronal death. In a photothrombotic stroke model, an H₂O₂ surge induces astrogliosis, glycosylation remodeling, and COL1 expression, leading to glial barrier formation, neuronal loss, and neurological deficits. These pathological cascades are mitigated by astrocyte-specific silencing of COL1 or FUT8 or by KDS12025, a peroxidase enhancer that reduces H₂O₂ burden. Notably, KDS12025 exerts potent neuroprotection in a non-human primate stroke model. Together, our findings identify an unprecedented astrocytic metabolic pathway linking oxidative stress to glycosylation-driven COL1 production, highlighting the H₂O₂ surge, astrocytic COL1, and FUT8 as promising therapeutic targets for recovery after stroke.