Anthocyanins and prebiotics have been shown to impact overall health and wellness. One mechanism for the health benefits has been through modulation of the microbiome and the intestinal ecosystem. The objective of this study was to determine the effects of a supplement containing both anthocyanins and prebiotics on modulating the intestinal environment, including the microbiome and intestinal inflammation. Fifty‐one healthy, obese male and female participants with BMI from 29.2 to 40.6 kg/m2 and between 20 and 60 years of age were enrolled in an 8‐week long open‐label single‐cohort study. Participants maintained their normal dietary and lifestyle habits and abstained from consuming anthocyanin‐rich foods and prebiotic supplements from four weeks prior to enrollment and for the duration of the study. The supplement, in powder form, contained an anthocyanin blend from black rice, black currant, and blueberry extracts (total of 215 mg anthocyanins) and a blend of prebiotic fibers (2.7 g) and was consumed once daily. Clinical chemistry and hematology and vital signs were documented for safety measurements at baseline and after 8‐weeks of supplementation. Participants completed a daily bowel habits diary commencing seven days prior to enrollment and the duration of the study. Stool samples were collected within 48 hours prior to baseline and end‐of‐study visits to measure microbiome diversity and fecal calprotectin, a marker of intestinal inflammation. After 8 weeks of consuming the supplement daily, participants had a significant decrease in the phylum Firmicutes (p<0.001) and Actinobacteria (p<0.001), a significant increase in the phylum Bacteroidetes (p<0.001), a significant decrease in the Firmicutes to Bacteroidetes ratio (p<0.001) to be more similar to lean individuals, and a trend toward decrease in fecal calprotectin (p=0.107), compared to baseline. Bloating (p<0.05), gas (p=0.035), and abdominal pain severity (p=0.015) were significantly reduced and Bristol Stool Form Scale score was significantly improved during the study (p<0.05). The supplement was found to be safe and well tolerated based on vital signs and blood parameters. We found that consumption of a supplement containing a blend of anthocyanins and prebiotics positively modulated the intestinal ecosystem, including the microbiome, and provided insights into the mechanisms of action of the anthocyanin prebiotic formulation and its impact on health benefits. The study was registered on ClinicalTrials.gov (#NCT02743195).Support or Funding InformationSupported by Nu Skin Enterprises, Provo, Utah