Glucose-dependent insulinotropic polypeptide (GIP), a 42-amino-acid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, which fosters neuronal proliferation and preserves against cell death, which plays a crucial role when faced with neurodegenerative diseases like Alzheimer's and Parkinson's. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell models, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the EPAC/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for neurodegenerative disorders and aging-related pathologies.