The objective of this study is to synthesize neem-silver nitrate nanoparticles (neem-AgNPs) using aqueous extracts of Azadirachta indica A. Juss for malaria therapy. Neem leaves collected from FRIM Malaysia were authenticated and extracted using Soxhlet extraction method. The extract was introduced to 1 mM of silver nitrate solution for neem-AgNPs synthesis. Synthesized AgNPs were further characterized by ultraviolet-visible spectroscopy and the electron-scanning microscopy. Meanwhile, for the anti-plasmodial activity of the neem-AgNPs, two lab-adapted Plasmodium falciparum strains, 3D7 (chloroquine-sensitive), and W2 (chloroquine-resistant) were tested. Red blood cells hemolysis was monitored to observe the effects of neem-AgNPs on normal and parasitized red blood cells. The synthesized neem-AgNPs were spherical in shape and showed a diameter range from 31-43 nm. When compared to aqueous neem leaves extract, the half inhibitory concentration (IC50) of the synthesized neem-AgNPs showed a four-fold IC50 decrease against both parasite strains with IC50 value of 40.920 µg/mL to 8.815 µg/mL for 3D7, and IC50 value of 98.770 µg/mL to 23.110 µg/mL on W2 strain. The hemolysis assay indicates that the synthesized neem-AgNPs and aqueous extract alone do not have hemolysis activity against normal and parasitized red blood cells. Therefore, this study shows the synthesized neem-AgNPs has a great potential to be used for malaria therapy.