We reported a case involving a patient diagnosed with major depression with associated burning mouth syndrome (BMS) and tinnitus who was successfully treated with vortioxetine. The case was 57-year-old Japanese woman diagnosed with major depression according to DSM-5. She experienced increased levels of stress when performing daily duties. Her dominant symptoms were depressive mood, anxiety, restlessness, insomnia, loss of appetite, difficulty of concentration, general fatigue, BMS, and tinnitus. She complained of pain as well as tongue and oral mucosa discomfort. She also experienced tinnitus, which she described as sounding like the buzz of cicadas. To treat symptoms, 20 mg/day duloxetine was initially administered, which was gradually increased to 40 mg/day. Depressive mood, restlessness, loss of appetite, and general fatigue were moderately ameliorated with treatment; however, symptoms such as anxiety, insomnia, and loss of concentration persisted. Vortioxetine (10 mg/day) was added to duloxetine and clonazepam therapy. Within 2 weeks, duloxetine and clonazepam treatments were gradually tapered, and the dosage of vortioxetine prescribed was increased to 20 mg/day. Her BMS completely disappeared, and her glossodynia relieved.