Food allergies, particularly peanut allergies, are on the rise, affecting ∼10% of the U.S. population and 17% of adults. We explored sex-based differences in inflammatory responses to peanut allergens using a mouse model. Female mice exhibited severe allergic symptoms and a greater drop in body temperature than males when challenged with peanut extract and cholera toxin. Females showed higher levels of interstitial macrophages and neutrophils, while males showed increased eosinophil and lymphocyte influx. Elevated cytokines (IL-4, IL-5, and IL-9) in females correlate with increased IgE and histamine, indicating heightened mast cell activation. Reduced expression of the circadian gene Rev-erbα in female intestines post-challenge suggests a link between inflammatory responses and circadian disruption. IgE/mast cell and IgG/neutrophil-mediated pathways appeared to be involved in female responses. These findings suggest that hormonal and circadian influences may play critical roles in sex-based differences in peanut allergen, with further investigation needed to elucidate the underlying mechanisms.