The aim of this study was to enhance the risperidone delivery to the brain through the transnasal route via optimization of cubosomal gel. Cubosomes were prepared using glycerol mono-oleate (GMO), Pluronic F127 (PF127) and Tween 80 (T80). The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro drug release and transmission electron microscopy. Central composite design was planned for the formulae optimization and the selected formula (containing PF127 with concentration 15 mg/g GMO and T80 with concentration of 20mg/L) was re-prepared in presence of gelling polymer (gellan gum or polyox). The optimal cubosomal gel (containing 0.4% w/v polyox) had been subjected to ex-vivo permeation, histopathological evaluation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control (drug solution and/or suspension). Finally, the cubosomal gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.