The objective of the present research was to study the effect of two different polymers such as Guar gum and Tara gum and two different fillers such as Microcrystalline cellulose (Avicel PH 101), Dicalcium phosphate in formulation of a sustained release (SR) matrix tablet of Quetiapine fumarate. Quetiapine fumarate and polymer compatibility studies were performed using Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). The pre-compression mixture formulation was evaluated for flow ability and compressibility. The tablets were prepared by direct compression method. The effect of concentration and type of polymers, type of diluent on in-vitro drug release and release kinetics was studied extensively. FT-IR and DSC studies revealed no interaction between Quetiapine fumarate and polymers. Flow ability and compressibility study of pre-compression powder formulation showed that these formulations were within the theoretical range for processing into tablet dosage form. In-vitro drug release studies exhibited that the drug release was sustained up to 12 h for SR matrix tablets prepared with both Guar gum and Tara gum but Guar gum showed better sustained action with good percent drug release when compared with Tara gum. Hence both type of polymers mentioned above can be used for the preparation of SR tablets of Quetiapine fumarate.