This study aims to prepare and optimize Montelukast beta-Cyclodextrin loaded liposomal gels using Stat-Ease Design Expert Software (DX11). The effect of major independent variables (cholesterol, Poloxamer 188, and Span 80) on globule size, refractive index, % CDR, viscosity, gel strength and spreadability were studied using a 3-factor, 2-level Box-Behnken design. Montelukast beta-Cyclodextrin loaded liposomal gels were prepared. Various parameters were characterized include, globule size, refractive index, % CDR, viscosity, gel strength and spreadability. Data were analyzed using factorial design to obtain analysis of variance (ANOVA), regression coefficients and regression equation. Optical microscopy was employed to study morphology of the formulations. FTIR and HPLC studies were also performed.