Aim: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. Methods: Artemether-loaded nanoparticles (AAN) were designed and antimalarial activity evaluated in-vitro/in-vivo using Plasmodium falciparum/Plasmodium berghei species, respectively. Results: Selective internalisation of AAN into Plasmodiuminfected RBCs in preference to healthy erythrocytes was observed using confocal-imaging.In-vitro studies showed 50% dose reduction for AAN as compared to drug-only controls to achieve IC50 levels of inhibition. The nanoparticles exhibited 2-fold higher peak drug concentrations in RBCs with antimalarial activity at 50% of therapeutic doses in P.bergeiinfected mice. Conclusion: HSA-based nanoparticles offer safe and effective approach for selective targeting of antimalarial drugs.