Down syndrome (DS), caused by trisomy 21, affects 1 in 600-1000 live births and is associated with distinctive physical features, cognitive impairment, and oral health challenges such as increased susceptibility to dental caries, periodontal disease, and elevated prevalence of oral Candida spp. Barriers to dental care necessitate comprehensive strategies to address the unique oral health needs of children with DS. The aim of the study was to evaluate the effectiveness of a sugar-free probiotic oral rinse versus 0.2% chlorhexidine digluconate in reducing oral Candida albicans (OCA) counts and improving oral health outcomes in children with DS. A double-blind randomized controlled trial (CTRI/2022/10/046847) enrolled 30 children with DS (aged 6-14 years). Baseline evaluations included OCA quantification and oral health assessments (OHI-S and PHP). Following individualized oral rehabilitation, participants were randomized to either a probiotic rinse (Group 1) or chlorhexidine rinse (Group 2) for 2 weeks. OCA and oral health parameters were assessed at baseline (T), 2 weeks post-rehabilitation (T), 2 weeks post-rinse (T), and 6 months post-rinse (T). Both groups showed significant improvements in OHI-S and PHP scores (p < 0.05). The probiotic group demonstrated significantly lower OCA counts than the chlorhexidine group at T and T (p = 0.001). Hence, the probiotic oral rinse can be considered a safe, effective method for reducing OCA and improving oral health outcomes in children with DS, advocating its inclusion in oral health management strategies for this population.