In this study, the mechanical properties of human dental structures have been investigated by using instrumented nanoindentation. Immersion in solutions containing Streptococcus mutans, which is the principal cause of dental caries, was applied to tooth specimens to clarify its effect on the microstructure and mechanical properties of the dental structures. With an extended time of up to 16 h, the pH value of the S. mutans solutions dropped from 7.3 to 5.8. Therefore, after immersion in the S. mutans solutions for 16 h, slight erosions of the dental structures began; after 64 h, severe tooth decay occurred with obviously etched dental features. After 128 h, the elastic modulus of enamel and dentine dropped to 85 and 67%, respectively, of the original values of untreated specimens, and the hardness dropped to 88 and 55%, respectively.