Background: Chronic cerebral hypoperfusion (CCH) induces mild cognitive impairment and contributes to the progression of vascular dementia and Alzheimers disease. Hydrogen has demonstrated protective effects against various neurological disorders. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, plays a significant role in this context. This study aimed to investigate the impact of saturated hydrogen-rich saline (HRS) on cognitive deficits and explore potential mechanisms following CCH. Methods: CCH was induced in rats via two-vessel occlusion, and the animals were subsequently treated with saturated HRS. Cognitive function was assessed using the Morris water maze. The neuronal morphology and number in the hippocampus were evaluated through hematoxylin and eosin (H&E) staining, Nissl staining, and immunofluorescence of neuronal nuclear protein (NeuN) and microtubule-associated protein 2 (MAP2). Neuronal ultrastructure was observed under a transmission electron microscope. Lipid peroxide biomarkers were measured to estimate lipid peroxide injury. Iron accumulation was detected using Perls Prussian Blue (PPB) staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to determine iron metabolism and ferroptosis-associated factors. Mechanism validation involved the administration of Ferrostatin-1, Erastin, and RAS-selective lethal 3 (RSL3), inhibitors of ferroptosis, cystine/glutamate antiporter (System Xc^-) and glutathione peroxidase 4 (GPX4), respectively. Results: HRS reduced cell death in the hippocampal region of CCH rats, restored the ruptured outer mitochondrial membrane of neurons, and increased levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), GPX4, and solute carrier family 7 member 11 (SLC7A11), while decreasing Malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE). Additionally, iron deposition was reduced in HRS-treated CCH rats. HRS inhibited ferroptosis, as evidenced by upregulation of ferritin light chain (FTL) and ferritin heavy chain (FTH1), and down-regulation of transcription factor (TF), transferrin receptor 1 (TFR1), solute carrier family 11 member 2 (DMT1), Iron responsive element binding protein 2 (IREB2), and prostaglandin-endoperoxide synthase 2 (PTGS2). The inhibition of ferroptosis induced by HRS was mimicked by Ferrostatin-1. Erastin or RSL3 simulated CCH-induced neuronal injury and ferroptosis, which were alleviated by HRS. Conclusion: HRS improved cognitive impairment by suppressing ferroptosis in hippocampal neurons through the System Xc^-/GSH/GPX4 pathway following CCH, suggesting its potential as a novel therapeutic agent for CCH treatment.