Scientific evidence of susceptibility to dental caries in the population with Down Syndrome (DS) is limited and conflicting, making it difficult to establish firm conclusions. The aim of this systematic review and meta-analysis was to obtain scientific evidence of the possible association between dental caries and individuals with DS, compared to individuals without DS (control). An electronic search of five databases was performed, with no language or publication date restrictions. The studies were selected by two independent reviewers (Kappa = 0.83). The systematic review included 13 studies, while eight studies were included in the meta-analysis. The studies are presumably all at risk of bias given their observational character. Two of these evaluated the presence or absence of caries in permanent and deciduous teeth, and six evaluated the mean DMFT index in permanent teeth. Combined odds ratios (OR), standard difference, standard error and a 95% confidence interval (CI) were obtained. The vast majority of the studies found that individuals from control groups had more carious lesions or caries experience than those with DS. The results were statistically significant in seven studies (p<0.05). Meta-analysis of two studies revealed that individuals with DS had a lower dental caries than those in the control group (OR = 0.36; 95% CI = 0.22-0.57). In six studies, individuals with DS had a significantly lower mean DMFT index than individuals from the control group (Sd = -0.18; SE = 0.09; 95% CI = -0.35--0.02). The quality of the studies varied and in general had a high risk of bias. Scientific evidence suggests that individuals with DS have fewer dental caries than individuals without DS.