The present study discusses possibility of targeting an anti-Alzheimer’s drug rivastigmine tartarate (RT) to the brain using novel synthesized L-lactide-depsipeptide polymeric nanoparticles (NPs). Single emulsion-solvent evaporation technique was used for preparation of NPs. The mean particle size, zeta potential and entrapment efficiency of drug loaded NPs were found to be 142.2 ± 21.3 nm, +4.85 mV and 60.72 ± 3.72% respectively. Pharmacodynamic study showed faster regain of memory loss in amnesic rat with RT loaded NPs as compared to RT solution. In pharmacokinetic study, total concentration and mean residence time was increased up to 3.79 fold and 2 fold respectively while clearance was decreased to 1.91 fold on intravenous administration of RT loaded NPs as compared to RT solution. The biodistribution study demonstrated 5.45 fold and 2 fold increase in brain concentration of drug after administration of RT loaded NPs (i.v; 10.52 ± 1.31 ng/ml) as compared to plain RT solution by oral (1.93 ± 1.23 ng/ml) and intravenous (5.34 ± 1.22 ng/ml) route, respectively. Therefore, RT loaded L-lactide-depsipeptide polymeric NPs might be a potential drug delivery system in treatment of Alzheimer’s disease. Copyright © 2014 American Scientific Publishers.