Down syndrome (DS) is an autosomal disorder associated with mental and physical involvement. The typical craniofacial phenotype and the dental anomalies in DS subjects have been widely described, but a systematic report on the manifestations affecting the oral mucosae in children with DS is still lacking. This systematic review aimed to establish the prevalence of oral mucosal manifestations in children/young adults with DS. Pubmed, Web of Science, and Scopus were investigated in September 2020. Documents in English on DS children/young adults (up to 25 years) reporting oral mucosal findings were considered. Study quality was assessed with ROBIN-I. Of the 150 references retrieved, 14 studies were considered eligible. The risk of bias ranged from low to unclear. Fissured tongue appeared to increase with age and was more prevalent in DS children than in the general population. Lip fissures and cheilitis were heterogeneously reported. Candida spp. carriage with and without active candidiasis was more frequent in DS children/young adults than in controls. C. albicans was the most prevalent species. Few other oral mucosal conditions have been reported sporadically. The heterogeneity of the works revealed the need for more appropriate oral examination to intercept the oral manifestations of oral mucosa and prevent recurrent candidiasis.