Down syndrome is commonly associated with craniofacial and oral anomalies, including macroglossia, maxillary hypoplasia, and neuromuscular dysfunction, which may contribute to early tooth loss and complete edentulism. Prosthodontic rehabilitation in these patients represents a significant clinical challenge due to anatomical, functional and behavioral limitations. This report presents the clinical management of a 40-year-old male patient with Down syndrome and moderate intellectual disability who presented with complete edentulism. The patient was rehabilitated with conventional bi-maxillary complete dentures using adapted clinical protocols. Treatment complexity was increased by macroglossia, muscular hypotonia, dyskinetic movements, and reduced patient cooperation. Therefore, several modifications were implemented throughout the treatment process, including simplified impression techniques, the use of functional border molding adapted to patient tolerance, careful jaw relation recording, and a customized approach to tooth arrangement to enhance prosthesis stability and retention. Behavioral management strategies and shorter clinical sessions were also essential to ensure treatment acceptance. The outcome demonstrated satisfactory functional and aesthetic results, with improved mastication, phonation and patient comfort. This case highlights the importance of individualized prosthodontic approaches, clinician flexibility, and regular follow-up in managing patients with special needs, ultimately contributing to improved oral function and quality of life.