Nowadays, hyperlipidemia and abnormal triglyceride levels are global problems menacing human health worldwide. The objective of this study is in-vitro reduction of plasma triglyceride level of the human blood using quercetin through batch adsorption, process optimization, and enzyme-based photometric investigations. The molecular dynamic simulation was also employed to study the peroxidase inhibition effects of quercetin through the enzymatic assay. The best response to the objective function (final triglyceride concentration in the range of 120–170 mg/dl) was obtained at the optimal conditions i.e., contact time of 63 ± 2 min, shaking rate of 264 ± 0.2 rpm and adsorbent dose of 0.037 ± 0.001 g, using experimental design, response surface methodology. Optimization results indicated that quercetin dosage is the most important variable affecting triglyceride removal. Various adsorption isotherms and kinetic models were evaluated to describe the adsorption process. Langmuir type II and Freundlich isotherms as well as pseudo-second-order kinetic model fitted the experimental data appropriately. Based on inhibitory studies and molecular dynamic simulations, quercetin might adsorb plasma triglycerides and inhibit peroxidase enzyme.