Cold plasma is emerging as a novel food processing technology, with demonstrated efficacies for microbial inactivation and residual chemical dissipation of food products. Given the technology's multimodal action it has the potential to reduce allergens in foods, however data on the efficacy and mechanisms of action are sparse. This study investigates the efficacy of cold plasma on major peanut allergens (Ara h 1 and Ara h 2). For this purpose, dry, whole peanut (WP) and defatted peanut flour (DPF) were subjected to an atmospheric air discharge using a pin to plate cold plasma reactor for different treatment durations. With increases in plasma exposure, SDS-PAGE analysis revealed reduced protein solubility of the major peanut allergens. Alterations in allergenicity and structure of Ara h 1 and Ara h 2 were examined using ELISA and circular dichroism (CD) spectroscopy. Competitive ELISA with proteins purified from plasma treated WP or DPF revealed reduced antigenicity for both Ara h 1 and Ara h 2. The highest reduction in antigenicity was 65% for Ara h 1 and 66% Ara h 2 when purified from DPF. Results from CD spectroscopy analysis of purified proteins strongly suggests the reduction in antigenicity is due to modifications in the secondary structure of the allergens induced by plasma reactive species. Cold plasma is effective at reducing peanut protein solubility and causes changes in allergen structure leading to reduced antigenicity.