Orofacial myofunctional therapy (OMT) is an alternative form of treatment of obstructive sleep apnea (OSA), that incorporates various exercises to optimize tongue placement and increase oropharyngeal tone. The objective of this systematic review and meta-analysis is to determine the efficacy of OMT in OSA patients. PubMed/Medline, EMBASE, Cochrane, Web of Science. Using PRISMA guidelines, a directed search strategy was performed for randomized control trials (RCTs) published prior to March 24, 2023, featuring 10+ patients with OSA undergoing mono-therapeutic OMT. The primary outcome of interest was apnea-hypopnea index (AHI). Secondary outcomes included subjective sleepiness, sleep-related quality-of-life, and snoring frequency. Of the 1244 abstracts that were identified, 7 RCTs involving 310 patients met inclusion criteria. Adult OMT patients had a statistically significant improvement in AHI (MD -10.2; 95% CI, -15.6, -4.8, p < 0.05), subjective sleepiness (Epworth Sleepiness Scale; MD -5.66; 95% CI, -6.82, -4.5, p < 0.05), sleep-related quality-of-life (Pittsburgh Sleep Quality Index; MD -3.00; 95% CI, -4.52, -1.49, p < 0.05), and minimum oxygen saturation (MD 2.71; 95% CI, 0.23, 5.18, p < 0.05) when compared with sham OMT or no therapy. Within the single RCT featuring pediatric OMT patients, patients had poor compliance (<50%) and did not show any improvements in AHI, minimum oxygen saturation, or snoring frequency. OMT may provide a reasonable alternative for OSA patients who cannot tolerate CPAP or other more established treatment options. OMT benefits appear limited in children due to poor compliance. More studies are required to evaluate compliance and the long-term effects of OMT on OSA outcomes. 1 Laryngoscope, 134:480-495, 2024.