Two-piece mandibular advancement devices (MAD) are considered more comfortable than monoblock devices, and they are commonly used for the treatment of obstructive sleep apnea (OSA). However, they are not without limitations, especially in patients with nasal obstruction/malocclusion. Here, we discuss the case of a 37-year-old woman with mandibular regression and severe OSA, for whom a standard twopiece MAD was not adequetely effective. However, her sleep apnea improved with concurrent treatment with lip-muscle training (orofacial myofunctional therapy, OMFT) and a two-piece oral appliance (OA) supplemented with an elastic retention band (ERB). The OMFT improved lip muscle strength. In particular, the ERB restricted mouth opening. The application of OMFT together with an OA and ERB was a good option for this patient. Future clinical trials should include a three-arm study involving the OMFT (with measurement of lip-closure force, reflecting the degree of mouth opening), the two-piece OA with an ERB, and combined treatment.