The brain-derived neurotrophic factor (BDNF) is associated with emotional and cognitive functioning, and it is considered a transdiagnostic biomarker for mental disorders. Literature on insomnia related BDNF changes yielded contrasting results and it has never been synthetized using meta-analysis. To fill this gap, we conducted a systematic review and meta-analysis of case-control studies examining the levels of peripheric BDNF in individuals with insomnia and healthy controls using the PRISMA guidelines. PubMed, Scopus, Medline, PsycINFO and CINAHL were searched up to Nov 2022. Nine studies met the inclusion criteria and were assessed using the Newcastle-Ottawa Scale. Eight studies reported sufficient data for meta-analysis. Random-effects models showed lower BDNF in subjects with insomnia (n = 446) than in controls (n = 706) (Hedge’s g = −0.86, 95% CI: −1.39 to −0.32, p = .002). Leave-one-out sensitivity analysis confirmed that the pooled effect size was robust and not driven by any single study. However, given the small sample size, the cross-sectional nature of the measurement, and the high heterogeneity of included data, the results should be cautiously interpreted. Progress in the study of BDNF in insomnia is clinically relevant to better understand the mechanisms that may explain the relationship between disturbed sleep and mental disorders.