<p>Neuronal cholecystokinin (CCK) is the most abundant neuropeptide in the mammalian brain and serves as a critical neuromodulator regulating the physiological states of animals. Previous research on CCK primarily focused on its roles in digestive function, satiety regulation, and emotional modulation, while its involvement in the development of brain diseases remains largely unexplored. Interestingly, recent studies have revealed that CCK-2 receptor antagonists have significant effects on neural modulation, suggesting a potential strategy for the treatment of brain disorders such as Alzheimer’s disease, depression, and motor neuron disease, among others. To elucidate the neural effects of CCK on the progression of neurological disorders, we review the available evidence on the neuropeptide CCK in brain diseases at multiple levels and propose novel and complementary approaches to the treatment of brain diseases based on recent developments.</p>