Considering various merits associated with the nasal mucosa such large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism, and ready accessibility leads to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. Buspirone hydrochloride niosomal in-situ nasal gel was formulated, optimized and evaluated with the aim to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimizedusing32 factorial design. The niosomes were characterized for particle size, zeta potential, entrapment efficiency and in-vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for formation of in-situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. Ex-vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49 % w/w drug permeated after 8 h. The SEM and Zeta potential studies showed formation of good and stable vesicles. Thus, the application of niosomes proved the potential for intranasal drug delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug of delivery for Buspirone hydrochloride has been successfully developed.