To investigate the beneficial properties associated with polyphenols, we screened 12 polyphenols for their ability to increase the viability of PC12 cells subjected to oxidative stress via CoCl2 and H2O2. Cell viability data demonstrate that 50 micromol/L methyl gallate and 50 micromol/L fisetin significantly increase viability of H2O2-stressed cells. Further, viability data suggest that 100 micromol/L epigallocatechin gallate (EGCG) increases basal viability, but has no rescue effect on cells stressed with CoCl2 or H2O2. Analysis of intracellular reactive oxygen species (ROS) shows that EGCG, methyl gallate, and gallic acid are effective in reducing CoCl2-derived ROS, and that methyl gallate is effective in attenuating H2O2-derived ROS. Examination of nitric oxide concentrations shows that methyl gallate significantly increases nitric oxide, both in nonstressed and H2O2-stressed cells, whereas EGCG results are consistent with the scavenging of nitric oxide under nonstressed and stressed conditions. Furthermore, analysis of total glutathione levels reveals that EGCG, methyl gallate, and gallic acid pretreatments with and without H2O2 stress have the ability to significantly alter glutathione metabolism. These findings suggest that EGCG, methyl gallate, and gallic acid may have potential therapeutic properties.