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The major pathological feature of Alzheimer’s disease (AD) is the aggregation of amyloid β peptide (Aβ) in the brain. Inhibition of Aβ42 aggregation may prevent the advancement of AD. This study employed molecular dynamics, molecular docking, electron microscopy, circular dichroism, staining of aggregated Aβ with ThT, cell viability, and flow cytometry for the detection of reactive oxygen species (ROS) and apoptosis. Aβ42 polymerizes into fibrils due to hydrophobic interactions to minimize free energy, adopting a β-strand structure and forming three hydrophobic areas. Eight dipeptides were screened by molecular docking from a structural database of 20 L-α-amino acids, and the docking was validated by molecular dynamics (MD) analysis of binding stability and interaction potential energy. Among the dipeptides, arginine dipeptide (RR) inhibited Aβ42 aggregation the most. The ThT assay and EM revealed that RR reduced Aβ42 aggregation, whereas the circular dichroism spectroscopy analysis showed a 62.8% decrease in β-sheet conformation and a 39.3% increase in random coiling of Aβ42 in the presence of RR. RR also significantly reduced the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, ROS production, and apoptosis. The formation of three hydrophobic regions and polymerization of Aβ42 reduced the Gibbs free energy, and RR was the most effective dipeptide at interfering with polymerization.