BCAA metabolism plays a critical role in metabolic health and disease. Dietary restriction, particularly reduced protein intake, is associated with improved longevity and metabolic health by modulating pathways such as mTORC1 and AMPK. However, BCAAs, which constitute ~25% of dietary protein, may contribute to aging and metabolic disorders. This review explores the regulation of BCAA metabolism in tissues and its impact on metabolic health and disease in mammals. BCAAs are metabolized through enzymes such as BCAT and BCKDH, which convert them into intermediates that enter the TCA cycle or are used for fatty acid and glucose production. BCAA catabolism is regulated by phosphorylation and transcriptional factors like KLF15 and PPARγ. Impaired BCAA catabolism is linked to metabolic disorders such as diabetes, heart disease, and obesity. For example, reduced BCAA catabolism in adipose tissue is associated with insulin resistance and obesity, while BCAA catabolism in brown fat helps regulate energy homeostasis. BCAA metabolism is also crucial for brain function, as BCAAs contribute to neurotransmitter synthesis and energy production. Deficiencies in BCAA catabolism can lead to neurological disorders, such as maple syrup urine disease (MSUD), which is caused by mutations in BCKDH complex genes. Treatment involves BCAA-restricted diets or liver transplantation. BCAA restriction has shown benefits in metabolic health, including improved insulin sensitivity and glucose tolerance. A BCAA-restricted diet can improve metabolic health in mice and humans, particularly in those with type 2 diabetes. However, the effects of BCAA restriction on lifespan and healthspan vary by sex, with male mice benefiting more than females. Individual BCAAs, such as isoleucine and valine, may have distinct effects on metabolic health. Restricting isoleucine and valine improves metabolic health in mice, while leucine is more closely linked to mTORC1 signaling and cellular growth. BCAA restriction may be a promising therapeutic strategy for metabolic disorders, but further research is needed to understand its mechanisms and long-term effects.BCAA metabolism plays a critical role in metabolic health and disease. Dietary restriction, particularly reduced protein intake, is associated with improved longevity and metabolic health by modulating pathways such as mTORC1 and AMPK. However, BCAAs, which constitute ~25% of dietary protein, may contribute to aging and metabolic disorders. This review explores the regulation of BCAA metabolism in tissues and its impact on metabolic health and disease in mammals. BCAAs are metabolized through enzymes such as BCAT and BCKDH, which convert them into intermediates that enter the TCA cycle or are used for fatty acid and glucose production. BCAA catabolism is regulated by phosphorylation and transcriptional factors like KLF15 and PPARγ. Impaired BCAA catabolism is linked to metabolic disorders such as diabetes, heart disease, and obesity. For example, reduced BCAA catabolism in adipose tissue is associated with insulin resistance and obesity, while BCAA catabolism in brown fat helps regulate energy homeostasis. BCAA metabolism is also crucial for brain function, as BCAAs contribute to neurotransmitter synthesis and energy production. Deficiencies in BCAA catabolism can lead to neurological disorders, such as maple syrup urine disease (MSUD), which is caused by mutations in BCKDH complex genes. Treatment involves BCAA-restricted diets or liver transplantation. BCAA restriction has shown benefits in metabolic health, including improved insulin sensitivity and glucose tolerance. A BCAA-restricted diet can improve metabolic health in mice and humans, particularly in those with type 2 diabetes. However, the effects of BCAA restriction on lifespan and healthspan vary by sex, with male mice benefiting more than females. Individual BCAAs, such as isoleucine and valine, may have distinct effects on metabolic health. Restricting isoleucine and valine improves metabolic health in mice, while leucine is more closely linked to mTORC1 signaling and cellular growth. BCAA restriction may be a promising therapeutic strategy for metabolic disorders, but further research is needed to understand its mechanisms and long-term effects.