Background <p>Allergic rhinitis (AR) affects ~ 40% of the global population and is linked to IgE-mediated immunologic response. Group 2 innate lymphoid cells (ILC2s) exert a pivotal function in AR pathogenesis. Calcitonin gene-related peptide (CGRP) serves as a conduit between neural and immune regulatory pathways. Our objective was to explore the impact of calcitonin gene-related peptide (CGRP) on the proliferative capacity and functional characteristics of ILC2s in the context of AR.</p> Methods <p>Fifteen AR patients were recruited. Nasal lavage fluid (NLF) and peripheral blood mononuclear cells (PBMCs) were collected. ILC2s were sorted and stimulated with CGRP, IL-33, and VX745. The proliferation and function of ILC2s were determined.</p> Results <p>A significant elevation in CGRP protein levels was observed in NLF of AR patients compared to healthy controls. CGRP positively correlated with IL-5, IL-13 expression, and total nasal symptom score (TNSS). CGRP upregulated Calcrl and Ramp1 mRNA expression in ILC2s and stimulated their proliferation and GATA-3, RORα expression. However, CGRP alone did not affect type 2 cytokine secretion by ILC2s.</p> Conclusion <p>Targeting CGRP to inhibit proliferation of ILC2s may be a viable therapeutic strategy for treating AR.</p>