Neochlorogenic acid is a natural compound isolated from various fruits and vegetables that has anti-inflammation and anti-oxidative effects in macrophages. Inflammatory immune cells and tracheal epithelial cells can stimulate airway hyperresponsiveness, inflammation, and reactive oxygen species. In this study, we investigated the effect of neochlorogenic acid in ameliorating inflammatory and oxidative responses in asthmatic mice. We used an ovalbumin (OVA)-induced mouse model, treating mice with neochlorogenic acid by intraperitoneal injection. We also treated inflammatory human tracheal epithelial (BEAS-2B) cells with neochlorogenic acid to evaluate inflammatory cytokine levels and oxidative responses. The results demonstrate that neochlorogenic acid attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia in the lungs of asthmatic mice. Neochlorogenic acid also reduced type 2 cytokine expression in bronchoalveolar lavage fluid and improved oxidative stress in the lung. Neochlorogenic acid effectively blocked monocyte attachment to adherent BEAS-2B cells, and reduced pro-inflammatory cytokine and reactive oxygen species production in inflammatory BEAS-2B cells. These findings suggest that neochlorogenic acid is a potential immunomodulator that can ameliorate airway hyperresponsiveness and airway inflammation in asthmatic mice.