Polygonatum, commonly known as Solomon’s Seal, has a long history of use in traditional medicine systems, particularly in Traditional Chinese Medicine (TCM) and Korean herbal medicine. In these systems, Polygonatum species (such as Polygonatum sibiricum and Polygonatum odoratum) are primarily used as tonics to nourish Qi, moisten dryness, and support vitality, especially for symptoms such as fatigue, weakness, and aging. While these symptoms may overlap with those of depression, there is no clear documentation in classical texts or ethnobotanical records that Polygonatum was specifically or primarily prescribed for depression as defined in modern medical terms. Instead, its use for supporting mood or emotional well-being is indirect and based on its general restorative properties. Scientific studies investigating Polygonatum’s effects on depression are scarce, with only limited in vitro or animal studies suggesting possible neuroprotective or adaptogenic effects, but no strong clinical evidence exists to support its use for depression. Therefore, the justification for using Polygonatum in depression is based on traditional practice, with very limited and indirect supporting evidence.