Terrestrial D-amino acids have been found as either free amino acids or the components of peptides and proteins. The proteins originally comprising L-amino acids sometimes change into the D-amino acid-comprising form following natural epimerization. The resulting peptides and proteins have different physical, chemical, and/or biological properties from the original forms. Looking at the oligopeptide region of proteins, the hydrophobicity of oligopeptides has been calculated using semiempirical methods. The oligopeptides partly comprising D-amino acids mostly have more hydrophobic regions than the oligopeptides comprising only L-amino acids. This research focuses on the epimerization and isomerization of aspartic acid residues of the segments in the wild type and Italian mutant of Amyloid β42 to estimate the relationship between the epimerization and the hydrophobicity change. Higher hydrophobicity is known to facilitate the aggregation and toxicity of Amyloid β42 and its mutants. This research used a linear relationship between experimental log P and calculated log P (Clog P) in which log P is the logarithm of the partition coefficient P in 1-octanol to water. The calculation using semiempirical methods (PM5) validated the relationship between the structure change and the hydrophobicity during the epimerization of the oligopeptides. The epimerization at the two common aspartic residues, D¹ and D⁷ for the wild type and the Italian mutant, gave smaller Clog P values than non-epimerized ones. The epimerization at another common residue D²³ showed larger Clog P for the hexapeptide segments. Clog P values of the epimerized hexapeptide segments of the Italian mutant were larger than those of the wild type. The results suggest that the original and D-epimer at D²³ of the Italian mutant must be more hydrophobic than those of the wild type. The estimation agrees with the experimental results of aggregation.