The aim of this investigation was to describe the craniofacial and oral characteristics of children and/or adolescents with and without Down syndrome (DS). A bibliographic search of the Medline database (via PubMed), Scopus and SCIELO was performed using the keywords “craniofacial characteristics”, “dental characteristics” and “Down syndrome”. Systematic reviews, observational cross-sectional and longitudinal studies were included. On the contrary, case reports, letters to the editor, editorials and opinion articles were excluded. 251 articles were recovered, and only 30 fulfilled the selection criteria. DS patients were characterized by reduced dimensions of the maxillary bone, mandible, and skull base, compared to normal patients. Likewise, some of these abnormalities influenced more frequent presentation of a class III malocclusion in these patients. On the other hand, this population group showed a higher prevalence of periodontal diseases, less risk of dental caries, and the presence of alterations in the tongue, lips, dental development and palate morphology. The quality of life of these individuals is affected by difficulties in swallowing, talking, eating or breathing through the nose. In conclusion, the craniofacial and oral characteristics of DS patients present various alterations compared to healthy patients, and these alterations have a negative impact on their quality of life.