•Adiponectin is a cytokine secreted by adipose tissue with insulin-sensitizing, anti-inflammatory and anti-atherogenic effects.•Adiponectin may be a useful biomarker for understanding mental illness-metabolic syndrome comorbidity.•An inverse association between adiponectin levels and examined mental disorders was found.•Patients with an anxiety disorder; trauma or stressor-related disorder or bipolar disorder had significant lower adiponectin levels compared to healthy adults. Anxiety, mood, trauma- and stressor-related disorders confer increased risk for metabolic disease. Adiponectin, a cytokine released by adipose tissue is associated with these disorders and obesity via inflammatory processes. Available data describing associations with mental disorders remain limited and conflicted. A systematic search was conducted for English, peer-reviewed articles from inception until February 2019 that assessed for serum or plasma adiponectin levels in adults with an anxiety, mood or trauma-related disorder. Diagnoses were determined by psychiatric interview, based on DSM-IV, DSM-5 or ICD-10 criteria. Analyses were performed using STATA 15 and Standardized mean difference (SMD) with 95% confidence interval was applied to pool the effect size of meta-analysis studies. In total 65 eligible studies were included in the systematic review and 30 studies in this meta-analysis. 19,178 participants (11,262 females and 7916 males), comprising healthy adults and adults with anxiety, mood and trauma-related disorders, were included. Overall results indicated an inverse association between adiponectin levels and examined mental disorders. Specifically, patients with an anxiety disorder (SMD  = −1.18 µg/mL, 95% CI, −2.34; −0.01, p  = 0.047); trauma or stressor-related disorder (SMD  =  −0.34 µg/mL, 95% CI, −0.52; −0.17, p  = 0.0000) or bipolar disorder (SMD  =  −0.638 µg/mL, 95% CI, −1.16, −0.12, p  = 0.017) had significant lower adiponectin levels compared to healthy adults. Heterogeneity, potential publication bias, and lack of control for important potential confounders were significant limitations. Peripheral adiponectin levels appear to be inversely associated with anxiety, mood, trauma- and stressor related disorders and may be a promising biomarker for diagnosis and disease monitoring.