The goal of the investigation was to study the protective effects of the SWGEDWGEIW (the single peptide, TSP) from soybean peptides (SBP) on hydrogen peroxide (H 2 O 2 )-induced apoptosis together with mitochondrial dysfunction in PC-12 cells and their possible implications to protection mechanism. Meanwhile, the SBP was used as a control experiment. The results suggested that SBP and TSP significantly ( p < 0.05) inhibited cellular oxidative damage and ROS-mediated apoptosis. In addition, SBP and TSP also enhanced multiple mitochondrial biological activities, decreased mitochondrial ROS levels, amplified mitochondrial respiration, increased cellular maximal respiration, spare respiration capacity, and ATP production. In addition, SBP and TSP significantly ( p < 0.05) raised the SIRT3 protein expression and the downstream functional gene FOXO3a. In the above activity tests, the activity of TSP was slightly higher than that of SBP. Taken together, our findings suggested that SBP and TSP can be used as promising nutrients for oxidative damage reduction in neurons, and TSP is more effective than SBP. Therefore, TSP has the potential to replace SBP and reduce neuronal oxidative damage.