Studies conducted in rodents have highlighted that neurobiological processes underlying cognition and affect are modulated by the gut microbiota. Certain dietary fibers are able to modulate the composition of gut microbiota and are thus considered prebiotics. A review of the impact of the available prebiotic intervention studies in humans on cognition and affect, addressing the potential mediating role of the microbiota, was conducted. PubMed, Scopus, and PsycINFO were selected as sources. Fourteen articles were eligible for narrative synthesis. Data extraction and quality assessment were performed with characteristics established a priori. Some chronic prebiotic interventions (>28 d) improved affect and verbal episodic memory compared with a placebo. Acute prebiotic interventions (<24 h) were more efficient in improving cognitive variables (eg, verbal episodic memory). Future research should measure microbiota using adequate methodologies and recruit patients with dysbiosis, inflammation, or psychopathology. More research is needed to unravel the conditions required to obtain effects on affect and cognition.