In this study, we probed the molecular mechanisms of metabolic biomarkers and pathways affected by the bioactive ingredient geniposide (GP), which was shown to protect against experimental allergic rhinitis in mice. The methods used here involved a metabolomics strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-TOF/MS). Using the metabolomics strategy, serum samples of mice in control, model and GP groups were used to explore the differential production of metabolites and pathways related to defense activity of GP towards allergic rhinitis. Allergic symptom, inflammatory factors, and cell populations in the mice spleens were reversed by GP treatment. Seventeen potential biomarkers were discovered in experimental allergic rhinitis mice. GP was shown to have a regulatory effect on 12 of them, which were associated with 8 key metabolic pathways. The ingenuity pathway analysis platform was used to further understand the relationship between metabolic changes and pharmacological activity of GP. The pathways which affected by GP involved cellular growth and proliferation, organismal development, and free radical scavenging. This metabolomics study produced valuable information about potential biomarkers and pathways affected by GP during its effective prevention and therapeutic targeting of allergic rhinitis.