Flavonoids are dietary non-nutrient bioactives with antioxidant and anti-inflammatory properties. Fruits, vegetables, nuts, legumes, and tea are rich in flavonoids. After consumption, flavonoids are extensively metabolized by the gut microbiota and host tissues. Flavonoid metabolism exhibits extensive variation between individuals. It is plausible that inter-individual differences in flavonoid metabolism impact the immune system. Pre-clinical studies have characterized direct and indirect mechanisms by which flavonoids modulate intestinal immune function. This includes modulation of T cell differentiation, alteration of gut microbiota, and modulation of cytokines. Defining the importance of these mechanisms to human chronic disease will improve dietary recommendations for the anti-inflammatory uses of flavonoids.