Little is known about the effects of acrylamide (AMD) on the stomach. So, this study evaluated the effect of oral AMD exposure (20 mg/kg b.wt) on oxidative status, apoptotic, and inflammatory reactions in rat’s stomach for 60 days. To explore novel targets of AMD toxicity, a more detailed molecular and immune-expression study was performed. Besides, the possible protective effect of green synthesized zinc oxide nanoparticles (G-ZNP) (10 mg/ kg b.wt) was explored. The results revealed that AMD significantly provoked oxidative and lipid peroxidative damage of the stomach in terms of increased ROS and MDA but reduced SOD, CAT, GSH, and GSH/GSSG. Additionally, the stomachs of AMD-exposed rats showed a significant increment of PGE2 but reduced NO. Histopathologically, AMD induced a significant increase in PAS stain and the immunoexpression of iNOS and NF- κB in the glandular stomach. A significant upregulation of CART, VACHT, EGFR, caspase-3, NOS-1, and miR-27a- 5p was evident in the stomach of the AMD group. Yet, G-ZNP oral dosing significantly rescued the AMD-induced oxidative damage, apoptotic reaction, inflammatory effect, and altered miR-27a-5p and gene expressions in the stomach. Conclusively, these findings demonstrated the efficacy of G-ZNP in protecting against the harmful impacts of acrylamide on stomach tissues.