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A rapid and novel microwave-mediated protocol was established for extracellular synthesis of metallic silver (Ag) and zinc oxide (ZnO) nanoparticles using the extracts of macro-algae Gracilaria edulis (GE) and also examined its anticancer activity against human prostate cancer cell lines (PC3). The formation of silver nanoparticles (GEAgNPs) and zinc oxide nanoparticles (GEZnONPs) in the reaction mixture was determined by ultraviolet-visible spectroscopy. The synthesized Ag and ZnO nanoparticles were characterized by X-ray diffraction, Fourier transform infra-red spectroscopy, energy dispersive X-ray, and field emission scanning electron microscopy. The silver and zinc oxide nanoparticles were spherical and rod-shaped, respectively. Cell viability assays were carried out to determine the cytotoxic effects of AgNPs and ZnONPs against PC3 and normal African monkey kidney (VERO) cell line. The inhibitory concentration values were found to be 39.60, 28.55, 53.99 μg/mL and 68.49, 88.05, 71.98 μg/mL against PC3 cells and Vero cells for AgNPs, ZnONPs, and aqueous G. edulis extracts, respectively, at 48 h incubation period. As evidenced by acridine orange/ethidium bromide staining, the percentage of the apoptotic bodies was found to be 62 and 70 % for AgNPs and ZnONPs, respectively. The present results strongly suggest that the synthesized ZnONPs showed an effective anticancer activity against PC3 cell lines than AgNPs.