Celiac disease - a prevalent food intolerance - requires strict adherence to a lifelong gluten-free (GF) diet as the only effective treatment. However, GF products often lack soluble fibre and have a high glycaemic index. Consequently, there is a pressing need in the food industry to develop GF products with improved nutritional profiles. In this context, the impact of incorporating orange peel flour (OPF) into muffins undergoing sourdough fermentation was examined, focusing on their technological, antioxidant, and nutritional characteristics. The functional properties of OPF were investigated using human colon carcinoma HCT8 cells as a model system. Treatment with OPF extract demonstrated a notable reduction in malignant cell viability and intracellular ROS levels, indicating potent antioxidant capabilities. Western blot analysis revealed significant alterations in key signalling pathways, including increased phosphorylation of NF-kB at serine 536 and reduced intracellular levels of caspase-3, alongside increased phosphorylation of RIPK3 and MLKL, suggesting potential involvement in necroptosis. OPF incorporation in muffins with sourdough increased antioxidant activity, reduced glycaemic index, and affected the volatile profile. Furthermore, based on simulated colonic fermentation, muffins with OPF showed a slight prebiotic effect, supported by the significant increase in bacillus-shaped lactic acid bacteria and Clostridia population. Overall, OPF-enriched muffins demonstrated considerable antioxidant effects and impacts on cell viability, underscoring their potential as functional ingredients in GF products. These findings signify the prospect of OPF enhancing the nutritional profiles and conferring health benefits of GF muffins.