Distal-less homeobox 2 (Dlx2) is a member of the homeodomain family of transcription factors and is important for the development of cranial neural crest cells (CNCCs)-derived craniofacial tissues. Previous studies revealed that Dlx2 was expressed in the cementum and a targeted null mutation disrupted tooth development in mice. However, whether Dlx2 overexpression may impair in vivo tooth morphogenesis remains to be elucidated. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to identify the dental phenotypes in mice by observation, micro-computed tomography and histological examination. The Dlx2-overexpressed mice exhibited tooth abnormalities including incisor cross-bite, shortened tooth roots, increased cementum deposition, periodontal ligament disorganization and osteoporotic alveolar bone. Therefore, Dlx2 overexpression may alter the alveolar bone, cementum and periodontal ligament (PDL) phenotypes in mice.