Background and aims: Metabolic syndrome (MetS) and lipid abnormalities can increase the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aims of this study were to assess branched-chain amino acids (BCAAs) levels in MetS patients and to evaluate the effects of these acids on lipid profile abnormalities. Material and Methods: A cross-sectional study design comprising 30 normoglycemic lean subjects, 30 MetS patients, and 30 MetS-pre/T2DM patients was conducted to measure the BCAA levels for each of these groups. Then, an in vivo evaluation of BCAA hypolipidemic activity using Triton WR- 1339-induced hyperlipidemia was conducted in rats. Results: The BCAAs plasma levels showed a substantially significant increase in both MetS and MetS-pre/T2DM groups compared with lean normoglycemic controls. Furthermore, BCAAs in Triton WR-1339 treated rats could exert fenofibrate-like pronounced TC, TG, and LDL-C reductions but marked the HDL-C enhancements significantly. Conclusion: MetS is associated with the high plasma level of BCAAs, indicative of a putative predictive/prognostic value with respect to MetS patients. Moreover, BCAAs supplementation may serve as a potential novel therapeutic agent for the treatment of hyperlipidemia.