Ten important plant parts routinely used in South Indian ethnic food preparation as spices and condiments were investigated for their potential antidyslipidemic properties. The aim of the study was to characterize the biochemical properties of the polyherbal formulation (nutritional supplement) and evaluate its use to control dyslipidemia in patients. Phytochemical evaluation, in vitro α-amylase inhibitory assay, and high performance thin layer chromatography (HPTLC) fingerprinting were carried out with alcoholic extracts of all 10 individual plants and with the nutritional supplement. Investigation in human volunteers was conducted to evaluate the effect on dyslipidemia as measured by serum lipid biomarkers. Sixty-five volunteers were recruited for this study. Biomarker values at baseline and at 6th visit (end of review, 8/9 months) were compared to assess the usefulness of the nutritional supplement in the normalization of lipid biomarkers. In the qualitative analysis of metabolites, the results revealed the presence of various bioactive primary and secondary metabolites that might be responsible for their medicinal attributes. In human volunteers, after supplement intake along with standard therapy, we observed significant decrease in serum cholesterol, triglyceride, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels. High-density lipoprotein (HDL) level did not change in test patient volunteers. Reductions in hemoglobin A1C (HBA1C) and postprandial blood sugar levels were observed; the difference was not statistically significant. We believe that the polyherbal formulation of 10 medicinal plants has potent antidyslipidemic activity. Our results contribute for the first time toward documentation of augmented dyslipidemia control by use of the formulation. © 2017 Taylor & Francis Group, LLC.