Background: An imbalance between oxidative and reductive processes within cells can result in oxidative stress leading to a decrease in cellular survival. Use of natural products with antioxidant properties may reduce this oxidative stress. Objective: The objective of the study is to determine whether a natural product blend of turmeric, pagoda tree seed pod (quercetin), and rosemary (TQR) extracts can protect human liver cells from oxidative stress-induced cytotoxicity. Materials and Methods: HepG2 cells were treated with a blend of botanical extracts of TQR (1:3:5, w: w:w) and expression of genes downstream of nuclear factor (erythroid-derived 2)-like 2 (NRF2) activation was measured. We also measured the ability of the extract blend to protect DNA and lipids from oxidative stress by measuring via the comet assay and 8-isoprostane production, respectively. Finally, we measured the effect of the extract blend on HepG2 cell protection against oxidative stress-induced cytotoxicity. Results: We provide evidence that the TQR blend activates the NRF2 pathway leading to DNA protection, a decrease in lipid peroxidation, and whole cell protection against oxidative stress. Conclusion: These results suggest that consuming a blend of TQR at the ratio of 1:3:5 could provide benefits against environmental stressors that increase exposure to reactive oxygen species.