Background and Aim: Down syndrome (DS) is a delayed physical and mental development caused by an abnormality in chromosome 21, resulting in the presence of three chromosomes (trisomy 21). Several methods of toothbrushing, such as the Scrub, Bass, Charters, Fone's, Roll, and Stillman's methods have been introduced. The aim of this study was to evaluate oral hygiene levels after toothbrushing with the Fone's and the modified Bass methods in children with DS. Materials and Methods: This interventional study comprised 15 children (10 boys and 5 girls) aged 7-12 years (purposive sampling). Oral hygiene was assessed using the Simplified Oral Hygiene Index (OHI-S) method introduced by Greene and Vermillion. The results were analyzed using Student's t-test. Results: Oral hygiene indices were 2.96 and 1.57 before and after using the Fone's method, respectively (P=0.00), and 2.55 and 2.16 before and after using the modified Bass method, respectively (P=0.00). A significantly increased level of oral hygiene was noted with the Fone's method (1.39) when compared to the modified Bass method (0.39) of toothbrushing (P=0.00). Conclusion: Both the Fone's and the modified Bass methods of toothbrushing can improve the oral hygiene of children with DS, with the Fone's method appearing to be more effective than the modified Bass method.