Aims: Oxidative stress is an imbalance in the pro-oxidant/antioxidant homeostasis, characterized by excess accumulation of reactive oxygen/nitrogen species (ROS/RNS) and free radicals that can be toxic for cells by initiating disruptive peroxidation reactions on cellular substrates such as proteins, lipids, and nucleic acids. Neurons have a high content of unsaturated fatty acids which are easily peroxidable by the elevated levels of ROS and RNS produced by brain oxygen metabolism, yielding isoprostanes among which 8-iso-PGF2α derived from arachidonic acid represents a stable marker of lipoperoxidation, in vivo. Numerous findings pointed to the protective role of natural products against oxidative stress in the brain. Methodology: In the present work we evaluated the effects of a natural formula containing bacopa extract, vitamin E, astaxanthin and phosphatidylserine on lipoperoxidation in rat brain cortex, both in vivo and in vitro. Results: The results demonstrate that the natural formula could reduce basal and hydrogen peroxide- and amyloid β peptide-induced oxidative stress, as evidenced by the reduction of 8-iso-PFG2α and ROS/RNS production in the rat brain. Conclusion: Results could account for a rational use of herbal products in the treatment of conditions characterized by increased burden of oxidative stress and defective antioxidant mechanisms, such as aging and neurodegenerative disorders.