Caloric Restriction (CR) is widely recognized for its health benefits, including delayed aging and neuroprotective effects in age-related Neurodegenerative Diseases (ND). The development of Caloric Restriction Mimetics (CRM) has addressed some of the negative aspects of CR, opening new avenues for research, particularly in neurodegenerative diseases. This review focuses on CRM compounds, their mechanisms of action in preventing and treating neurodegenerative diseases, and their application to Alzheimer’s disease, Parkinson’s disease, and polyglutamine disorders such as Huntington’s disease and cerebellar ataxia. The review also discusses the potential of CRM in future therapeutic strategies for traumatic brain injury, often resulting in long-term neurological deficits and cause of early neurodegenerative diseases.