Researchers have reported diverse mechanical properties (Young's modulus) of human tooth enamel from experiments and finite element simulations, because of the complicated microstructure, which contains variations in crystal orientations and non-homogeneous properties. Although past models have effectively considered the microstructural effects, appropriate conditions for introducing crystal orientations within enamel rods and the property variations between rods and the interrod enamel are still necessary.In this thesis, the micromechanical response of the enamel microstructure is investigated using a periodic finite element model to determine the effective monoclinic mechanical properties and determine localized effects of microstructure on the stress field. A spherical micro-indentation test was conducted on the bulk enamel model and the effective homogeneous model. The difference in response to indentation loading between the heterogeneous and homogeneous models revealed changes related to the enamel microstructure.The model can be used to consider changes in effective properties of enamel based on microstructural variations, which can be applied to restorative materials attached or embedded within enamel. The study of the influence of microstructure on the damage generation and failure modes of enamel can also be accomplished using the model, which may be due to fractures and the abrasion-erosion wear process.