The second-to-fourth digit ratio (2D:4D) is an indirect, retrospective, non-invasive measure that correlates negatively with intrauterine exposure to testosterone. The present meta-analysis aimed to evaluate if 2D:4D differs between patients with psychiatric disorders and controls. In September 2019, we searched in Web of Knowledge, PsycINFO, Embase, and CINHAL, and retrieved 619 papers. We finally included 43 case-control studies which compared the 2D:4D ratio of patients with autism spectrum disorder (ASD) (n = 16), schizophrenia (n = 8), gender non-conformity (n = 7), addictions (n = 5), attention deficit-hyperactivity disorder (ADHD) (n = 4), mood disorders (n = 2), and intellectual disability (n = 1) to non-clinical controls. Meta-analyses showed that, overall, psychiatric patients had lower 2D:4D than healthy controls (n = 43, overall sample = 9,484, mean difference = −0.0056, 95% confidence interval from −0.0093 to −0.002, I 2 = 74%), with more pronounced differences in the right hand, males, and children. Considering psychiatric disorders individually, significant differences were found in the ASD, ADHD, and addictions groups, in which 2D:4D was significantly lower than healthy controls. Conversely, the right hand of males with schizophrenia showed higher 2D:4D than healthy controls. No other significant differences were detected. Although our results need to be cautiously interpreted and find limited applications in clinical practice, they may suggest that 2D:4D is altered in some psychopathological conditions, underlining the role of prenatal exposure to sex steroids in the etiology of psychiatric disorders.