Current research work involves preparation of fast dissolving tablets of Losartan Potassium by direct compression method using different concentrations of Plantago ovata and Lepidium sativum mucilage as natural superdisintegrants. A two factor three level (32) factorial design is being used to optimize the formulation. Nine formulation batches (A1-A9) were prepared by taking two factors as independent variables (X1- amount of Plantago ovata mucilage and X2- amount of Lepidium sativum mucilage) were taken with three levels (+1, 0, -1). All the active blends were evaluated for precompression parameters (angle of repose, bulk density, carr’s index, hausner’s ratio) and formulated tablets were evaluated for post compression parameters (hardness, friability, weight variation, wetting time, disintegration time, water absorption ratio). In vitro drug release studies were carried out using USP II dissolution apparatus for 30 min. The software Design Expert (8.0.7.1) was used for generating experimental design, modeling the response surface and calculating the statistical evaluation. Tablet parametric tests of formulation batches (A1-A9) of FDT were found within prescribed limits. DT was observed in the range from 12±2 to 58.7±2.52 sec and WT from 10.3±1.52 to 49.7±5.13 sec for formulation batches (A1-A9). More than 87% drug release was observed in all formulation batches (A1-A9) within 15 minutes. Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (P < 0.05). Formulation A7 was selected by the design expert software which exhibited DT (22.15sec), WT (17.31sec) and in vitro drug release (100%) within 15 minutes.