In recent years, nanotechnology has become one of the most promising new approaches for pest control. In our screening program, laboratory trials were conducted to determine the effectiveness of five sources of silver nanoparticles (Ag NPs) and sulfur nanoparticles (S NPs) on larval, pupal, and adults of the fruit fly Drosophila melanogaster. Nanoparticles of silver and sulfur were synthesized through reducing, stabilizing, and capping plant leaf extracts method and different concentrations (10, 50, 100, 200 ppm) were tested on D. melanogaster. Results showed that silver nanoparticles (Ag NPs) were highly effective on larvae, pupae, and adults’ mortality and egg deterrence. On the contrary, none of the tested nanoparticles has a significant effect on pupae longevity. The results also showed that silver nanoparticles can be used as a valuable tool in pest management programs of D. melanogaster.