Backgound and Aims: Entire human race is now under the threat of Metabolic disorder pandemic. The current study evaluated a novel therapeutic efficacy of ferulic acid (FA), atorvastatin (AS) and their combined treatment against high fat diet (HFD) induced oxidative stress and non alcoholic steatohepatitis (NASH). Methodology: The swiss albino mice were administered HFD (52.37% fat, 11.4% of total energy, 33.6% carbohydrate from published protocol for 6 weeks. A robust experimental protocol with contemporary analytical tools were employed to validate the hypothesis. Statistical analysis: The values were given as Mean ± SEM. Statistical analyses were performed using one-way analysis of variance (ANOVA) with Tukey’s post hoc test using OriginPro2020 software. p < 0.05 was considered as the level of significance. Each data are representative of at least two independent biological repeats. Results: The HFD mice showed increased body weight, insulin resistance index, plasma and hepatic lipid profile, histological features of NASH with decreased phosphorylation of AMPK-α. HFD mice exhibited increased oxidative damage in liver concomitant with increased production of intracellular reactive oxygen species (ROS), lipid peroxidation with simultaneous inhibition of the antioxidant defence machinery. Increased liver apoptosis was noticed through the ROS induced apoptotic pathway, elicited by increased depolarization of the mitochondrial membrane, increased expressions of Cdc42, p-SAPK/JNK and Bax-Bcl2 ratio. There was relevant decrease in the phosphorylation status of the survival proteins like PI3K and Akt, synergistic to the decreased nuclear translocation of Nrf2. This study also tried to hone in to understand the status of the ROS mediated inflammatory pathway which showed increased nuclear translocation of NF-κB and simultaneous up-regulation of its downstream proinflammatory genes. Supplementation with FA or AS and unique combination of FA and AS in the diet significantly counteracted the HFD-induced inflammation and apoptotic effects. Innovation : our results showed for the first time that HFD induced oxidative damage to the liver and its apoptosis through the ROS mediated pathway which was ameliorated by FA, AS and their combination treatment. Conclusion: FA and AS or the unique combination of FA+AS conferred protection against HFD-induced oxidative stress, NASH and apoptosis by modulating Nrf2, NF-κB pathway.