Upcycling, or reincorporating waste into consumer goods, has become a spearhead for food sustainability. In addition to reducing waste, studies propose a nutritional benefit of consuming upcycled materials like grape byproducts. Grape skins and pulp contain phenolic compounds strongly associated with anti-inflammatory effects. However, grape byproducts have rarely been challenged in an inflamed in vivo system. Thus, this study assessed grape juice pulp and its impact on induced intestinal inflammation in vivo. We used the intra-amniotic administration (in ovo) model, which harnesses the broiler (Gallus gallus) embryo and its innate consumption of its amniotic fluid on day 17 of incubation. We took a novel double-injection approach where inflammation was induced by first injecting 0.75% dextran sodium sulfate (DSS) followed by a second injection of a 3% grape juice pulp extract (GJPE). Treatment groups were randomly assigned and adequately controlled (n=102 divided into six groups). To confirm the induction of inflammation and to assess gut health, we measured intestinal permeability via fluorescein isothiocyanate dextran (FITC-d) in the serum, duodenal claudin-1 and occludin expression via RT-qPCR, and duodenal morphology via histology. The FITC-d analysis revealed an ameliorative effect of GJPE on DSS-induced gut permeability. This was further supported by significant decreases in claudin-1 and occludin expression (p<0.05), suggesting that tight junction function was protected by GJPE. Finally, the histological analysis demonstrated significantly greater villus surface area, goblet cell size, and crypt depth (p<0.05) for inflamed groups receiving GJPE compared to the inflamed control. These results re-emphasize grape juice pulp’s potential to attenuate intestinal inflammation. Future long-term feeding trials are needed to confirm an anti-inflammatory effect of grape byproducts in the context of a full diet. Nevertheless, this study provides an important step towards upcycling grape waste streams for nutritional benefit.