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Mounting evidence indicates that mindfulness-based interventions improve physical and mental health. However, whether brief mindfulness intervention supports health benefits by regulating metabolic profiles is poorly understood. To address this gap, this randomized controlled trial compared ten 1-hour sessions of integrative body-mind training (IBMT) with relaxation training (RT) in 42 participants. Untargeted metabolomics was performed on fasting serum samples to investigate the physiological effects of the interventions on metabolic profiles. After IBMT, significant increases were observed in glycine derivatives, glutamate, and tetrahexosylceramide, while multiple sulfur containing compounds decreased. In contrast, RT yielded no significant intervention effects. A direct comparison between IBMT and RT revealed significant group differences in the levels of glycine, phosphatidylcholine, phosphatidylethanolamine, phosphoglycerol, phosphatidylserine, sphingomyelin derivatives, and α-linolenic acid. Further, pathway and enrichment analyses confirmed the effects of IBMT on amino acid and lipid metabolism with significant alterations to sphingolipid, α-linolenic acid, and linoleic acid metabolism as well as histidine and pyruvate metabolism. These findings suggest that IBMT can reprogram key metabolic pathways. In conclusion, this study offers insights into how a brief mindfulness intervention modulates metabolic profiles and highlights the potential of mindfulness-based interventions to promote health through metabolic regulation. These findings may guide the development of future mindfulness-based health promotion strategies.