Increased reactive oxygen species (ROS) production can activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and initiate the transcription of pro-inflammatory mediators, such as cytokines, leading to inflammatory diseases. The ability of fermented food to scavenge ROS and mitigate oxidative stress-related damage may represent a promising preventive and therapeutic strategy for the treatment of inflammatory bowel disease. The aim of this study is to investigate the antioxidant and anti-inflammatory potential of fermented wheat flour, with specific consortia of yeast and acid lactic bacteria strains, on intestinal cells by quantifying intracellular ROS levels and evaluating the expression of genes involved in inflammatory pathways. There were no significant differences in intracellular ROS levels after 24 and 48 hours of treatment with fermented and unfermented wheat flour compared to untreated cells. The effect of a 24-hour treatment with fermented and unfermented flour extracts on the modulation of genes involved in inflammation (IL-1, IL-6, and IL-8) and oxidative stress (HMOX-1) was evaluated by quantitative real-time PCR. The unfermented wheat flour extract increased the basal expression of IL-6 and IL-8 (*p<0.05) compared to fermented flour and untreated cells, respectively, while exposure to fermented wheat flour did not alter the basal expression of pro-inflammatory cytokines. Moreover, treatment with both flour extracts increased HMOX-1 expression. These findings suggest that fermented wheat flour does not induce a pro-inflammatory response in intestinal cells, unlike unfermented wheat flour, which increases IL-8 expression. Additionally, both fermented and unfermented flour extracts upregulate HMOX-1, indicating a potential role in oxidative stress modulation and supporting the possible benefits of fermented wheat flour in inflammatory bowel disease management.