A growing body of evidence supports the therapeutic effects of blueberry in neurodegenerative disorders. Biotransformation of blueberry juice by Serratia vaccinii bacteria increases its phenolic content and antioxidant activity. In neuronal cell culture, biotransformed blueberry juice (BJ) significantly increased the activity of antioxidant enzymes, namely catalase and superoxide dismutase. Moreover, BJ protected neurons against H2O2-induced cell death in a dose-dependent manner. This associated with the upregulation of mitogen-activated protein kinase (MAPK) family enzymes p38 and c-Jun N-terminal kinase (JNK) activation, as well as with the protection of extracellular signal-regulated kinase (ERK1/2) and MAPK/ERK kinase (MEK1/2) activity loss induced by H2O2. The present studies demonstrate that BJ can protect neurons against oxidative stress possibly by increasing antioxidant enzyme activities and activating p38- and JNK-dependent survival pathways while blocking MEK1/2- and ERK1/2-mediated cell death. Thus, BJ may represent a novel approach to prevent and to treat neurodegenerative disorders, and it may represent a source of novel therapeutic agents against these diseases.