Caloric restriction (CR) has been widely recognized as a robust intervention for extending lifespan and delaying the onset of age-related diseases across multiple species. However, long-term adherence to CR in humans poses significant practical and psychological challenges. This has increased interest in calorie restriction mimetics (CRMs), compounds that mimic the beneficial effects of CR without reducing caloric intake. CRMs target key cellular and molecular pathways involved in aging, such as AMP-activated protein kinases, sirtuins, and mammalian targets of rapamycin. By modulating these pathways, CRMs can enhance cellular stress resistance, improve metabolic health, and reduce inflammation hallmarks associated with aging and chronic diseases. Examples of well-studied CRMs include resveratrol, metformin, and spermidine, which show promise in preclinical and clinical studies for promoting healthy longevity. While the potential of CRMs is substantial, translating these findings into safe and effective human therapies requires a deeper understanding of their long-term effects, optimal dosing, and population-specific responses. Additionally, systems biology and personalized medicine advancements may pave the way for tailoring CRM-based interventions for individual aging trajectories. As research continues to evolve, CRMs hold promises for extending lifespan and enhancing health span, thereby contributing to healthier aging and reducing the burden of age-related conditions in the global population.