Coffee husks are the main by-product of the coffee industry and have been traditionally discarded in the environment or used as fertilizers. However, recent studies have shown that coffee husks have bioactive compounds, such as phenolics and fiber-bound macro antioxidants, offering a range of potential health benefits. This study evaluated the antioxidant capacity, cytoprotective/cytotoxic properties, and stimulatory effects on the relative abundance of selected intestinal bacterial populations of individuals with diabetes of organic coffee husks. Organic coffee husk had good antioxidant capacity, maintained under simulated gastric conditions, with more than 50% of antioxidant capacity remaining. Organic coffee husk exerted cytoprotective properties in Caco-2 cells, indicating that cellular functions were not disturbed, besides not inducing oxidation. Overall, organic coffee husk promoted positive effects on the abundance of distinct intestinal bacterial groups of individuals with diabetes during in vitro colonic fermentation, with a higher relative abundance of Bifidobacterium spp., indicating the availability of components able to reach the colon to be fermented by intestinal microbiota. Organic coffee husk could be a circular material to develop new safe and pesticide-free functional ingredients with antioxidant and potential beneficial effects on human intestinal microbiota.