Due to its high nutritional value and broad beneficial effects, the artichoke plant (Cynara cardunculus L.) is an excellent healthy food candidate. Additionally, the artichoke by-products are usually discarded even though they still contain a huge concentration of dietary fibers, phenolic acids, and other micronutrients. The present work aimed to characterize a laboratory-made gluten-free bread (B) using rice flour supplemented with a powdered extract from artichoke leaves (AEs). The AE, accounting for the 5% of titratable chlorogenic acid, was added to the experimental gluten-free bread. Accounting for different combinations, four different bread batches were prepared. To evaluate the differences, a gluten-free type-II sourdough (tII-SD) was added in two doughs (SB and SB-AE), while the related controls (YB and YB-AE) did not contain the tII-SD. Profiling the digested bread samples, SB showed the lowest glycemic index, while SB-AE showed the highest antioxidant properties. The digested samples were also fermented in fecal batches containing viable cells from fecal microbiota samples obtained from healthy donors. Based on plate counts, no clear tendencies emerged concerning the analyzed microbial patterns; by contrast, when profiling volatile organic compounds, significant differences were observed in SB-AE, exhibiting the highest scores of hydrocinnamic and cyclohexanecarboxylic acids. The fecal fermented supernatants were recovered and assayed for healthy properties on human keratinocyte cell lines against oxidative stress and for effectiveness in modulating the expression of proinflammatory cytokines in Caco-2 cells. While the first assay emphasized the contribution of AE to protect against stressor agents, the latter enlightened how the combination of SB with AE decreased the cellular TNF-α and IL1-β expression. In conclusion, this preliminary study suggests that the combination of AE with sourdough biotechnology could be a promising tool to increase the nutritional and healthy features of gluten-free bread.