Phytochemicals are compounds synthesized in plants that result from secondary metabolism. As a part of plant-rich diets, phytochemicals are associated with wide ranging health benefits including antioxidant, anticancer, antimicrobial, anticlotting, anti-inflammatory effects. There are a wide variety of intrinsic and extrinsic factors that determines the rate and degree of release of phytochemicals from food (bioaccessibility) and the fraction that is absorbed (bioavailability), which greatly impact their physiological functions. During digestion, phytochemicals undergo extensive structural modifications as modulated by pH changes, digestive enzymes and gut microbial catabolism. These digestive processes generated absorbable phytochemical metabolites that differ greatly in structure and bioactivities from the native form found in foods. This chapter will discuss the variety of factors that affect the gastrointestinal processing of phytochemicals at the gut level and how this can affect their health modulating properties.