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Allergic rhinitis (AR) is a prevalent global health concern with significant implications for public health.Current treatment approaches for AR patients have obvious concerns, which include various adverse effects, low remission rate, and less effective for those patients with unknown causing allergens. Thus, there is an urgent need to develop alternative therapeutic strategies that are both safe and effective for different allergens. In this study, we providedrobust evidence demonstrating that Lactobacillus plantarumGUANKE immunobiotic strain exerts its therapeutic effects by suppressing AR-associated cytokines and chemokineswhilerestoring epithelial barrier integrity. By using single-cell sequencing analysis, we further revealed that GUANKE inhibited Th2 cell differentiation in the nasal mucosa, thereby modulating the immune responses. Targeted metabolomics showed that GUANKE significantly increased levels of equol, indole-3-propionic acid (IPA), and phenylalanine metabolism as well.Additionally, we not only demonstrated that GUANKE has broad therapeutic effectsin improving nasal symptoms induced by two other allergens, mugwort and HDM, but also revealed that such therapeutic effects were attributed to the reduced levels of cytokines and chemokines as well as its inhibitory effect on Th2 cell differentiation.