Sensitivity to wheat and peanut proteins is widespread and is not restricted to geographical areas where wheat and peanuts are produced. It emphasizes the importance of these crops as the source of energy and proteins to populations globally. An uptick in the number of individuals diagnosed with celiac disease, an autoimmune disorder – and peanut allergy was observed in the last two decades. According to a recent estimate, ~1.4% of the world population is diagnosed with celiac disease and ~2% with peanut allergies. Unfortunately, there is no therapy available for these sensitivities other than a preventive diet with a need to maintain an immunogen-free environment to prevent sensitive individuals’ accidental exposure to the antigen. Given this knowledge, the present research focuses on developing reduced-immunogenicity wheat and peanut genotypes that can significantly reduce the scope of severe reaction to accidental exposure to wheat/peanut proteins. Working in this direction, we undertook two approaches to develop reduced-immunogenicity wheat/peanut genotypes: 1) wheat/peanut germplasm screening for genotypes with reduced immunogen content to crossbreed them to develop reduced to non-immunogenic wheat/peanut lines. 2) Use a CRISPR-based multi-gene editing approach to silence genes encoding major allergenic proteins. To achieve the first objective, we screened wheat landraces and peanut-mini-core collections. Similarly, to induce site-specific mutations, guide RNAs from the wheat gluten gene sequences and the peanut Ara h1, Ara h2, Ara h3, and Ara h6 gene sequences were developed and assembled in single guide RNA modules. The progress made on these objectives in both crops will be discussed.