This work presents an innovative nanocomposite aimed at enhancing medication delivery for the successful treatment of allergic rhinitis (AR). Quercetin (QU) and Perillyl Alcohol (PA) were co-encapsulated in a carboxymethyl chitosan (CMC) matrix to create nasal formulation. This nasal formulation aims to improve therapeutic effectiveness by circumventing first-pass metabolism, resulting in more rapid and potent effects. Optimized feed concentrations produced nanocomposites with appropriate absorbance, increased drug loading (QU: 96.75 %, PA: 97 %), and encapsulation efficiency. Particle size analysis indicated hydrated diameters of 212.5 ± 0.25 nm for QU, 153.0 ± 4.6 nm for PA and 122.9 ± 0.1 nm for QU/PA@CMC formulations, demonstrating satisfactory stability as determined by zeta potential. FT-IR and XRD validated the existence of functional groups and the degree of crystallinity. TEM and SEM imaging revealed cluster nanoparticles with negligible agglomeration. In vitro release showed markedly improved drug release from the nanocomposites relative to unencapsulated pharmaceuticals. In vitro hemolysis and cytocompatibility assays indicate that nanoformulations exhibit significant biocompatibility (95 %) and hemocompatibility (>5 %). In vivo investigations using an AR mice model shown that QU/PA@CMC therapy markedly decreased allergy symptoms, histamine concentrations, cytokine synthesis, and inflammatory cell infiltration in the nasal lavage fluid. The data indicate that QU/PA@CMC is a viable treatment approach for AR, enhancing effectiveness and safety through effective modulation of inflammatory responses. © © 2025. Published by Elsevier B.V.