Nowadays, polymeric nanoparticles have drawn more attention as drug carrier by investigators.In this study, we synthesized high selective imprinted nanoparticle polymer using olanzapine as template. The aim of this study was preparing efficient imprinted polymer nanoparticles from olanzapine as the template for the controlled release of olanzapine as a therapeutic drug for central nervous systems (CNS) disease at different pH values and the solid-phase extraction (SPE) as the sample clean-up technique combined with high-performance liquid chromatography (HPLC). The morphology of the nanoparticles was determined using scanning electron microscopy (SEM) images. Drug release, binding properties and dynamic light scattering (DLS) of the molecularly imprinted polymers (MIPs) were studied in this investigation. The adsorption isotherm was fitted with Langmuir and Freundlich models. The performance of the MIPs for the controlled release of olanzapine was assessed in two different media (SDS 1% and PBS). Results revealed that the MIPs have potential application in controlled drug release. Moreover, cytotoxicity of the MIP nanoparticles was measured on NIH/ 3 T3 cell line using MTT method.Furthermore, the MIPs were applied to extraction of olanzapine from human blood plasma samples. The limit of detection (LOD) and limit of quantification (LOQ) were evaluated and were 0.18 µg L -1 and 0.39 µg L -1 , respectively. These results collectively illustrate that MIP nanoparticles can be employed as an efficient technique for the extraction of the olanzapine from human plasma.