Abstract Context Biochemical markers correlate positively with the development and severity of obesity, depression, and anxiety, and can be modulated by changes in intestinal microbiota composition. Objective A systematic review and meta-analysis was conducted to determine the effects of prebiotics or synbiotics on blood biomarkers of obesity, depression, and anxiety (including: ACTH [adrenocorticotropic hormone], cortisol, leptin, ghrelin, TSH [thyroid-stimulating hormone], PTH [parathyroid hormone], vitamin D, BDNF [brain-derived neurotrophic factor], and PCR [polymerase chain reaction]) in individuals with overweight or obesity. Data Sources MEDLINE, Web of Science, Scopus, and CENTRAL databases were searched, along with the reference lists of included articles. Authors were contacted for unpublished data. Study Selection RCT in individuals with overweight or obesity, supplemented with prebiotics or synbiotics, assessing any of the outcomes of interest. Data Extraction Data were extracted independently by three researchers. Results Thirteen studies were identified up to March 7, 2018. Regarding outcomes, 1 study assessed leptin, 4 studies assessed ghrelin, and 10 studies assessed CRP (C-reactive protein). Meta-analysis showed reduction in serum concentrations of ghrelin (−37.17 pg/mL; 95%CI = −69.62, −4.73; P = 0.025) and CRP (SMD [standardized mean difference] = −0.31; 95%CI = −0.58, −0.04; P = 0.027) after supplementation of inulin-type fructans. Conclusions Prebiotics may help regulate blood concentrations of ghrelin and CRP in overweight or obese individuals.