Applications of the Drosophila melanogaster (D.m.) research model have an important means both for genetic investigations and for the study of metal toxicity, because D.m. has physiological mechanisms comparable to those in human organisms. In this research, the toxic effect of lead (Pb2+) and copper (Cu2+) on four D.m. genotypes—the wild genotype (Oregon-R, used as control) and three mutant genotypes (white, brown, and white-vestigial)—was compared. Five replicates were made to observe the development progress of monitorized genotypes exposed to five different concentrations 0, 0.50, 0.75, 1.00, and 2.00 mM of copper (CuSO4) and lead Pb(C2H3O2)2. Proliferation rates of larvae, pupae, and adults depend on genetic factors, metals used (copper or lead), and their concentrations. The white-vestigial mutant genotype showed the greatest sensitivity at IC50 concentration (inhibition of proliferation of more than 50% compared with the control sample) at doses of 1.00 mM for Cu2+ and 2.00 mM for Pb2+. In contrast, the control genotype (Oregon-R) showed only an inhibition IC50 concentration of 2.00 mM for Cu2+. The white-vestigial mutant genotype showed the greatest sensitivity at IC50 concentration (inhibition of proliferation of more than 50% compared with the control sample) at doses of 1.00 mM for Cu2+ and 2.00 mM for Pb2+. In contrast, the control genotype (Oregon-R) showed an inhibition at the IC50 concentration of 2.00 mM for Cu2+. The results conclude that (i) the dose influences the prolificacy rate in a directly proportional way, (ii) the comparative analyses between Cu2+ and Pb2+ revealed a more acute effect of Cu2+, and (iii) differentiated prolificacy values according to genotypes were recorded. Those reflect the importance of using D.m. as a research model in the comparative studies of the interactions between genetic factors and metal toxicity. Also, this study provides significant information on non-toxic maximum doses for organisms.