Objectives: This review investigated the effects of orthodontic or functional orthopedic therapy on masseter muscle thickness through the use of ultrasonography (US) in growing subjects when compared with untreated subjects. MaterialsandMethods: This review systematically assessed studies that investigated growing subjects undergoing orthopedic therapy for the correction of malocclusion of vertical, sagittal and transversal plane. Electronic databases (CENTRAL, MEDLINE-PubMed, Scopus and Web of Science) were searched up to February 2019, including available RCTs and CCTs, without language restrictions. The primary outcome was the effect of orthopedic or functional treatment on masseter muscle thickness. The risk of bias of included studies was assessed through the Newcastle-Ottawa quality assessment scale with the aim of defining their methodological quality. A random-effects meta-analysis analyzing mean differences with 95% confidence intervals was used for quantitative analysis. Results: The search retrieved 749 titles, but the studies selection resulted in a final sample of 5 CCTs. The studies retrieved data from 233 children (age range: 5-22 years) and were conducted at university dental clinics. Children were treated for Class II malocclusion, increased vertical dimension or lateral cross-bite variably with rapid or slow maxillary expansion, twin block, bite block, mandibular activators, quad helix, alone or in combination. Risk of bias was assessed as medium for three studies, low for one and high for another. The meta-analysis determined that at the end of orthopedic or functional treatment masseter muscle thickness, measured through the use of US, is significantly reduced (MD -0.79 mm; 95% CI -1.28 to -0.31). The reduction in muscle thickness, therefore, could be considered an indicator for the evaluation of the success of therapy with orthodontic appliances. Conclusions: Although the meta-analysis revealed that US could be considered a less invasive and effective method to evaluate the masseter muscle thickness, single-blinded RCTs, are required to confirm US reliability in this field of application. This review was registered on PROSPERO with the following registration number: CRD42018068402.