Plant food biofortification is recently receiving remarkable attention, as it aims to increase the intake of minerals, vitamins, or antioxidants, crucial for their contribution to the general human health status and disease prevention. In this context, the study of the plant's secondary metabolites, such as polyphenols, plays a pivotal role for the development of a new generation of plant crops, compensating, at least in part, the low nutritional quality of Western diets with a higher quality of dietary sources. Due to the prevalent immunomodulatory activity at the intestinal level, polyphenols represent a nutritionally relevant class of plant secondary metabolites. In this review, we focus on the antioxidant and anti-inflammatory properties of different classes of polyphenols with a specific attention to their potential in the prevention of intestinal pathological processes. We also discuss the latest biotechnology strategies and new advances of genomic techniques as a helpful tool for polyphenols biofortification and the development of novel, healthy dietary alternatives that can contribute to the prevention of inflammatory bowel diseases.