A highly sensitive and cost-effective HPTLC method was developed for the determination of rivastigmine hydrogen tartarate (RIV) in bulk and capsules. Moreover, magnetic solid phase extraction procedure (MSPE) was performed for analysis of RIV in human plasma to preconcentrate RIV and decrease interference from plasma constituents. The magnetic nanoparticles (MNPs) were prepared by co-precipitation process and characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), powdered X-ray diffraction (PXRD) and dynamic light scattering (DLS). These prepared MNPs have shown high extraction efficiency and all parameters affecting the adsorption of RIV on the MNPs were fully investigated. The method was validated according to FDA bio-analytical guidelines and was found to be linear over the range of 30.2–648 ng/spot. The LLOQ and LOD were 26.2 and 8.6 ng/spot, respectively.