Depression and other neuropsychiatric diseases are brain disorders that affect daily life. They are triggered by stress from changes in environment, relationships, finances, chronic illness, and other life obstacles. The number of patients with depression is on the rise worldwide, and in recent years, due to the COVID-19 pandemic, there is concern about a further increase. Oxidative stress (OS) plays an important role in depressive disorders in recent studies, including decreased serum antioxidant levels in depressed patients. Increased reactive oxygen species (ROS) and OS-induced dysfunction are associated with the etiology and progression of depression. However, at present, depression is commonly treated with many antipsychotic drugs, and few therapies have targeted oxidative stress. Twendee X®︎ (TwX), an antioxidant combination supplement with dementia-preventive effects for mild cognitive impairment (MCI) in Japanese, provides mitochondrial protection, maintains neurogenesis in the hippocampal dentate gyrus, increases brain autophagy and telomeres, in addition to antioxidant properties that cannot be achieved with a single ingredient. It is composed of eight vitamins, amino acids, and CoQ10, and has passed the same safety standards required of pharmaceuticals. In addition to lowering blood oxidative stress, TwX has been reported to improve quality of life, including defecation status and sleep quality, by acting on the gut microbiota. These various effects suggest that TwX is promising in terms of providing a new treatment option for neuropsychiatric disorders such as depression. Antioxidant therapy using effective antioxidant supplements is promising in terms of diversifying treatment methods in the treatment of depression, even in view of its different positioning from pharmaceuticals.