Nanoparticles can act as drug carriers that can modulate pharmacokinetics, increase bioavailability and target release with minimal toxic effects. The present work aimed to assess the therapeutic effect and electron microscopic changes of Nigella sativa loaded Chitosan Nanoparticles (NSLCN) on adult Schistosoma mansoni in vitro. Adult worms were removed from the portal and mesenteric veins of infected mice after 90 days, and then three to five mature worms including both sexes were cultured. Schistosoma adult was exposed to NSLCN at concentrations of (10, 20, 40, 60, 80, and 100 μg/ml) for 24, and 48 h. Examination for worm viability was done after 24, and 48 h using a stereomicroscope comparing with control negative and control positive groups. The mortality rate in worms reached 88.9% in the group treated with 100 μg and 80 and 84.6% in groups treated with 80 and 60 μg respectively (p-value <0.001). After 48 h of incubation with the same concentration, there were variable effects on motility and death of worms, the death rate reached 100% in all groups treated with nanoparticles. After 24 h incubation, the live worms have sluggish motility and reached dead score at 48 h of incubation. By (SEM) there were tegumental changes of both dead male and female in the form of loss of spines, swollen suckers and swollen inter tubercular ridges in male and loss of smooth architecture of female tegument with multiple pores. In conclusion, NSLCN appears as a new potential candidate drug against schistosomiasis. We successfully applied nanoemulsion preparation against the adult stage of S. mansoni in vitro.