Objectives The purpose of this clinical study was to evaluate the orthopaedic and dentoalveolar treatment outcomes of slow maxillary expansion (SME) using the expander with differential opening (EDO) in patients with cleft lip and palate (CLP). Material and methods Eight children with maxillary arch constriction and CLP in the mixed dentition were selected. The patients were treated with EDO. Cone-beam computed tomography (CBCT) scans were done prior to expansion and six months after the expansion. Alveolar crest width, maxillary alveolar width, buccal and palatal alveolar bone thickness of molars were assessed. Interphase comparisons were performed using paired t-tests (p<0.05). Results SME using EDO promoted significant increases in alveolar crest width, maxillary alveolar width, and palatal alveolar bone thickness of molars. Additionally, SME promoted a slight reduction of buccal alveolar bone thickness of molars. Conclusions In children with CLP, SME using EDO caused orthopaedic and dentoalveolar changes. Clinical relevance SME can be recommended to treat individuals with CLP who have a constricted maxillary arch in the mixed dentition. Trial registration The trial was registered at Clinicaltrials.gov under the identifier NCT04997083.