Spermidine is a natural polyamine that stimulates autophagy, a cellular process essential for degrading and recycling damaged organelles and proteins, thereby promoting cellular homeostasis and longevity. Autophagy plays a critical role in maintaining cellular function by removing harmful aggregates, reducing oxidative stress, and enhancing mitochondrial quality control, which are key factors in aging and age-related diseases. Research indicates that spermidine supplementation can extend lifespan and health span across various species, including yeast, nematodes, flies, and mice, by upregulating autophagy-related genes and pathways such as mTOR inhibition and AMPK activation. In humans, spermidine levels decline with age, and higher dietary intake of spermidine-rich foods has been associated with reduced overall mortality, particularly from cardiovascular diseases and cancer, suggesting that maintaining optimal spermidine levels through diet or supplementation may provide anti-aging and health-promoting benefits.