Background: Obesity is a chief cause of metabolic dysfunction and leads to type 2 diabetes, fatty liver diseases, hypertension, and cardiovascular complications. Obesity leads to insulin resistance. Hyperglycemia and hyperlipidemia cause an increase in reactive oxygen species (ROS) due to enhanced substrate-mediated cellular metabolism, the release of proinflammatory cytokines, and lipid peroxidation. The pathophysiology of non-alcoholic fatty liver disease (NAFLD) and its progression are influenced primarily by oxidative stress. Emerging evidence suggests that mitochondrial dysfunction leads to oxidative stress in NAFLD. Recent research suggests that activation of transient receptor potential vanilloid subfamily 1 (TRPV1; also known as capsaicin receptor) counters obesity and NAFLD. However, the mechanism underlying this remains unclear. This research addresses this knowledge gap. Experimental Approach: We used wild-type (WT) and TRPV1-/- mouse models to evaluate the effect of dietary capsaicin in countering High Fat Diet (HFD) induced NAFLD. These mice received a normal chow diet (NCD) or HFD (± capsaicin) for 32 weeks. We isolated the liver tissue from these mice and performed in vitro experiments. Key Results: Morphological/histological analysis showed that capsaicin ameliorated fatty liver in WT but not in TRPV1-/- mice. HFD feeding increased reactive oxygen species, lipid peroxidation, and caspase 3 activity while capsaicin feeding countered these in the liver isolated from WT but not in TRPV1-/- mice. Conclusion: Our results indicate that dietary capsaicin reduces lipid peroxidation and redox stress in the liver. We hypothesize that capsaicin-induced TRPV1 activation antagonizes HFD-mediated oxidative stress in NAFLD. Further studies to analyze the role of TRPV1 in preventing NAFLD are in progress.