As individuals with Down syndrome often suffer from oro-facial abnormalities which can affect their oral health as well as their and their family's quality of life, this link was examined in the present study. Using a descriptive cross-sectional design, 63 parents of children with Down syndrome who attended two special daycare centres in Riyadh, Saudi Arabia, were surveyed using a self-administered validated questionnaire. The findings yielded by the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) version 17 revealed that in 34.9% children and 46% of their families, quality of life was affected by oral health. Moreover, 54% children experienced physical pain, which was severe in 22.2% of the cases. Further analyses revealed that families' emotional lives were negatively affected by children's oral health status. Therefore, as oral health in children with Down syndrome exerts significant adverse impacts on different aspects of their lives and those of their families, timely provision of required oral health care is warranted.