Background. Sibjeondaebo-tang (SJDBT) has been used to treat diverse disorders including neuropsychiatric disabilities in traditional Korean medicine. Objective. The present study aims to investigate the potential effects of SJDBT on neuroprotection against Aβ peptide-induced damage using in vitro culture and in vivo rat brain systems. Materials and Methods. PC12 cell viability was analyzed by MTT assay, and neurite arborizations and caspase 3 protein signals in cultured PC12 cells and in vivo cortical neurons were analyzed by immunofluorescence staining. Phospho-Erk1/2 protein was analyzed by immunofluorescence staining and western blot analysis. Results. In PC12 cells, atrophied cell body and reduced neurite extension by Aβ treatment were recovered by SJDBT treatment. Caspase 3 protein signals were increased in Aβ-treated PC12 cells, but SJDBT treatment decreased apoptotic cell death. Caspase 3 activation in cortical neurons, which was induced similarly by Aβ treatment, was reduced by SJDBT treatment. Furthermore, phospho-Erk1/2 protein levels, which had been decreased by Aβ treatment, were elevated in the cortical neurons by SJDBT treatment. Conclusion. These data show that SJDBT may play a role in protecting from damages induced by Aβ in neuronal tissue and further suggest that SJDBT can be explored as the potential therapeutic target for AD treatments in human.