Abstract : The work aims at formulating nanostructured lipid carrier (NLC) of quetiapine fumarate in combination with curcumin to treat schizophrenia. The prominent scope is to optimize the concentration of lipids by design of experimental approach (DOE) and to formulate a stable nanostructured lipid carrier system. The lipids incorporated in this were cholesterol as solid lipid and oleic acid as liquid lipid, vitamin E TPGS plays its role as solublizer, stabilizer and a non -ionic surfactant. The formulations were optimized by response surface method. The 22 factorial design is employed for the sake of achieving the desired goal. NLC were prepared by hot homogenization followed by ultrasonication. The NLC formulations were subjected to diversified studies that comprises of entrapment efficiency, invitro release studies, size analysis, surface morphology and stability studies. The molecular docking analysis to know the binding of the formulation with D2 and DAT receptors. All the parameters of the study resulted in satisfactory results with the optimized formulation (QC-NLC-1) having particle size of 93nm with entrapment efficiency of 97.8% and invitro release rate of 93.7% of quetiapine fumarate and 63.59% of curcumin in 72 hours. The formulation was found to be stable with all its characteristics retained even after 180 days at 40±2°C/ 75±5% RH. In silico studies by molecular docking and ADMET revealed the docking of drug at various receptor level ensuring the formulated NLC penetrates BBB. In case of D2R, curcumin and quetiapine showed considerable binding affinity with free binding energies of -5.76 and -5.52 Kcal/mol respectively and had sufficient hydrogen bonding with receptors.