A great emphasis is currently given to the early correction of malocclusions to prevent further complications if left untreated. Interceptive orthodontics not only simplifies but also eliminates the need for later procedures. The 2 × 4 appliance is an orthodontic treatment modality applied during the mixed dentition period, particularly for malpositioned permanent upper incisors. This scoping review was aimed to examine the breadth and depth of the published literature on this clinical topic, as well as knowledge gaps, about this fixed appliance during mixed dentition, for the correction of incipient anterior malocclusions (incisor crowdings, midline diastemas, or crossbites). PubMed, Cochrane Library, Google Scholar, Dentistry & Oral Sciences Source, and two grey literature databases were explored; under a structured PICO question (Patient, Intervention, Comparison, Outcome) and eligibility criteria, for relevant clinical trials, observational studies, and case reports/series (in English or Spanish), using different searching terms. Titles and abstracts were screened. Full-text articles were critically reviewed for bias risk and a data charting table was constructed. 161 references were identified, after which 115 titles remained after removing duplicates. After the abstract screening, 18 potential full-text articles were reviewed. Finally, 16 studies were included, according to the performed critical appraisal. The 2 × 4 appliance is suitable for mixed dentition patients with mild or severe malocclusions, particularly when removable appliance usage is a critical problem.