Wheat is a fundamental staple crop worldwide, contributing significantly to global food security due to its versatility and nutritional value. However, gluten proteins, including gliadins and glutenins, have been implicated in various health problems, such as celiac disease, non-celiac gluten sensitivity, and wheat allergies. These disorders affect a wide variety of people globally, creating demand for wheat varieties that balance high-end-use quality with reduced immunogenic potential. This review examines the molecular and genetic mechanisms that regulate gluten protein synthesis, highlighting recent advances in genomic and mutagenic approaches aimed at modifying gluten proteins to enhance the health and quality traits of wheat. Technologies such as RNAi and CRISPR/Cas9 offer promising avenues for reducing wheat immunogenicity without compromising its functional properties in food production. This study also examines the challenges and prospects of utilizing these genetic tools to develop wheat varieties that achieve the dual objectives of enhanced health outcomes and high product quality.