S-equol is a major intestinally-derived bacterial metabolite of daidzein, one of the principal isoflavones found in soybeans and most soy foods. S-equol has a similar structure to estrogen, and binds to estrogen receptors to exhibit estrogenic activity. S-equol has been shown to bind to estrogen receptors (ER) α and β and to effectively activate both receptors, although with greater transactivation of ERβ. It has been proposed that the ability to make S-equol when soy is consumed may be an important factor in determining the clinical efficacy of a soy diet, the so-called “equol hypothesis”. Equol has many beneficial effects on menopausal women. However, equol production depends on the individual’s intestinal flora; and research has shown that only 30 to 50% of individuals in the populations studied are capable of producing equol from daidzein. A lactic acid bacterium, Lactococcus garvieae (Lactococcus 20-92 strain), with equol-producing capabilities was identified and isolated from human feces. Recently, we standardized the production of an S-equol supplement (SE5-OH) using this strain. Reports suggest that the S-equol supplement contributes positively to menopausal symptoms, bone health, metabolic syndrome and skin aging. In this paper, we introduce new insights into equol or SE5-OH based on epidemiological and clinical study.