Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) plays a significant role in neuroprotection and has been investigated for its potential in treating neurodegenerative diseases such as Parkinson’s and Alzheimer’s. It modulates neuronal survival, reduces inflammation, and promotes the release of neurotrophic factors, supporting brain cell function and repair. In migraine research, PACAP-38 is recognized as a key mediator. It is involved in vasodilation and activation of trigeminal pathways, making it a target for anti-migraine therapies. Antibodies and antagonists that block PACAP-38 or its receptors are under development for migraine prevention. PACAP-38 also influences metabolic regulation by enhancing insulin secretion and beta-cell survival, suggesting potential applications in diabetes management. Additionally, it contributes to stress response regulation through its action in the hypothalamus and adrenal glands, affecting hormone release and autonomic function. Its anti-inflammatory and tissue-protective effects are being explored in conditions like stroke, traumatic brain injury, and ischemia-reperfusion injury. Due to its broad receptor distribution, PACAP-38 holds promise in multiple therapeutic areas, especially where cell protection and modulation of nervous system activity are critical.