Modern approaches to management of medical conditions are based on a holistic view, taking into account bidirectional connections between physical and mental health. The current pharmacologically focused model has so far provided modest benefits in addressing the burden of poor mental health. Convincing data suggest that diet quality and select nutrient-based supplements might influence a range of neurochemical modulatory activities, improving the management of mental disorders. Examples of these nutrient-based supplements include omega-3 fatty acids, S-adenosyl methionine, N-acetyl cysteine, zinc, B vitamins (including folic acid), and vitamin D. The traditional Mediterranean diet is considered to be the most beneficial diet in our region. Based on the results of preclinical studies, we are increasingly aware of the role of intestinal microbiota in the pathogenesis and potential treatment of mental disorders. Bidirectional signalling between the brain and the gut microbiome involving vagal neurocrine and endocrine signalling mechanisms influences mental and physical wellbeing. These findings suggest that using prebiotics, probiotics or in the strict sense psychobiotics, as well as incorporating fermented foods in the diet, could have a potential role in the management of mental disorders. As of now, we lack sufficient evidence to implement recommendations for dietary supplements in treatment guidelines, however, this might change in light of emerging data from contemporary research studies, at least for certain indications.