The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold.