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Abstract In central nervous system cells, low molecular weight fractions (LMWF) from snake venoms can inhibit changes in mitochondrial membrane permeability, preventing the diffusion of cytochrome c to the cytoplasm, inhibiting the activation of pro‐apoptotic factors. Here, we evaluated the neuroprotective activity of LMWF from Bothrops jararaca (Bj) snake venom in H2O2‐induced cytotoxicity in cultured hippocampal cells. SDS‐PAGE, FT‐IR and MALDI‐TOF analysis of LMWF (<14 kDa) confirmed the absence of high‐molecular‐weight proteins in the fraction. LMWF did not present cytotoxicity in all concentrations and time tested by MTT assay. Neuroprotection was evaluated in cells pretreated with LMWF for 4 h prior to the addition of 50 &mgr;M H2O2 for 20 h. We demonstrated that LMWF reduced the argininosuccinate synthase (AsS) and superoxide dismutase (SOD1) expressions, suggesting that this fraction as an effective neuroprotective compound that could increase the hippocampal cells viability by attenuation of oxidative stress. In addition, LMWF protects against apoptosis induced by H2O2, reducing the expression of caspase‐3 and caspase‐8. Overall, this study opens new perspectives for the identification of new molecules for the development of drugs applied to the treatment of neurodegenerative diseases. HighlightsLow Molecular Weight fraction (LMWF) from B. jararaca has Bradykinin Potentiating Peptides.LMWF has neuroprotective activity against H2O2‐induced oxidative stress.LMWF inhibit the cell death H2O2‐induced.LMWF inhibit the expression of caspase‐3 and caspase‐8 H2O2‐induced.LMWF reduces the expression of SOD1 and AsS increased by H2O2.