Branched-chain amino acids play an important role in regulating glucose and lipid metabolism, protein synthesis, and lifespan. Many studies have reported that the level of circulating branched-chain amino acids or their dietary intake is closely associated with life expectancy, sarcopenia, obesity, and diabetes mellitus. In different animal models, branched-chain amino acids and lifespan are often found to have opposite effects. This paper reviews the biological characteristics of branched-chain amino acids and their two opposite functions and mechanisms in regulating lifespan to provide new insight into and a reasonable basis for the intervention of branched-chain amino acids on aging.