Down syndrome (DS) is an autosomal chromosomal disorder caused by trisomy of all or a critical part of chromosome 21. Individuals with DS have high levels of oxidative stress throughout their lifespan. It has been suggested that levels of antioxidants could be altered in response to an infection or disease. Aim: To assess the total antioxidant capacity (TAC), nitric oxide (NO), and sialic acid (SA) of saliva in children with DS and its relation to their oral health status. Materials and methods: Thirty-four noninstitutionalized children in the age group of 7–12 years having DS formed the study group. The control group consisted of 34 normal, healthy children. The W.H.O. criteria were used for diagnosis and recording of dental caries. Oral hygiene status was assessed using the simplified oral hygiene index. Estimation of TAC, NO, and SA levels in saliva was done. Data obtained were subjected to statistical analysis. Results: In comparison to normal children, DS children showed significantly lower TAC of saliva and significantly higher salivary SA levels. In both groups of children, dental caries was higher in primary dentition when compared to their permanent dentition.