Adult cleft lip and/or palate (CL/P) patients with a maxillomandibular skeletal discrepancy and missing teeth require an interdisciplinary approach for esthetic satisfaction. The prosthetic and orthodontic treatments for two unilateral CL/P patients with 2 different prostheses and orthodontic interventions are described. A 20-year-old woman with a skeletal Class II, anterior open bite, and the missing teeth was treated with zirconia-based fixed dental prostheses after orthodontic treatment with the intrusion of the maxillary molars using miniscrews. A 34-year-old man with a skeletal Class III, anterior crossbite, chronic generalized moderate periodontitis, and the defected area was treated with a dental implant, and zirconia-based fixed dental prostheses after periodontal treatment and bimaxillary surgery. These clinical reports demonstrate that prosthetic treatment combined with nonsurgical or surgical orthodontic treatment can be effective for adult patients with unilateral CL/P and missing teeth. The therapeutic approaches resulted in improvements in the patients’ facial appearances and satisfaction.