Elevated levels of BCAAs have been associated with heart failure and metabolic disease. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid) was designed to induce branched-chain amino acid (BCAA) oxidation to restore levels of BCAAs. BT2 treatment confers cardioprotection and protects from metabolic disease in preclinical models including mice subjected to trans-aortic constriction or LAD ligation, db/db mice, ob/ob mice, and Zucker fatty rats. However, mice with the BCKDK knocked out specifically in the heart or skeletal muscle does not protect from heart failure, suggesting an alternative molecular mechanism by which BT2 is conferring its protective effects. In this study, we provide evidence characterizing BT2 as a mitochondrial uncoupler. Using reductionist systems including respirometry, mitochondrial membrane potential, and patch-clamp electrophysiology, we demonstrate that BT2 is indeed uncoupling mitochondria and is approximately five-fold milder than the well-known chemical uncoupler DNP. Functional assays expose BT2’s protective effects originate from diminishing ROS production and reducing de novo lipogenesis. The evidence provided here more likely solves the long-standing question on BT2’s mechanism by which it is conferring therapeutic effects. Furthermore, these studies establish mild uncouplers of mitochondria as promising pharmacological agents for the treatment of cardiovascular and metabolic disease.