This review explores the role of short-chain fatty acids (SCFAs) in the gut-brain axis, particularly their potential to mediate interactions between the microbiome, gut, and brain. SCFAs, produced by bacterial fermentation of dietary fiber in the colon, are believed to influence psychological functioning, including affective and cognitive processes. The review summarizes existing knowledge on SCFA metabolism, their impact on cellular systems (such as histone deacetylase inhibition and receptor activation), and their effects on gut-brain pathways (immune, endocrine, and vagal). It also discusses the modulation of SCFA production through prebiotic, probiotic, and dietary interventions, and their potential role in neuropsychiatric disorders. Despite the growing interest in SCFAs, direct evidence linking them to psychological functioning remains limited, and future research is needed to clarify their mechanisms and effects. The review highlights the need for more studies to investigate the dose-response effects of SCFAs on various biological systems and to explore their impact on human psychological functioning.This review explores the role of short-chain fatty acids (SCFAs) in the gut-brain axis, particularly their potential to mediate interactions between the microbiome, gut, and brain. SCFAs, produced by bacterial fermentation of dietary fiber in the colon, are believed to influence psychological functioning, including affective and cognitive processes. The review summarizes existing knowledge on SCFA metabolism, their impact on cellular systems (such as histone deacetylase inhibition and receptor activation), and their effects on gut-brain pathways (immune, endocrine, and vagal). It also discusses the modulation of SCFA production through prebiotic, probiotic, and dietary interventions, and their potential role in neuropsychiatric disorders. Despite the growing interest in SCFAs, direct evidence linking them to psychological functioning remains limited, and future research is needed to clarify their mechanisms and effects. The review highlights the need for more studies to investigate the dose-response effects of SCFAs on various biological systems and to explore their impact on human psychological functioning.