Aims To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs). Design Systematic review and meta-analysis. Setting Clinical studies that evaluated peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls Participants SUD patients and healthy controls. Measurements PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta-analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random-effects model by the Comprehensive Meta-Analysis version 2 software. Findings Concentrations of interleukin (IL)-6) in 32 studies, tumor necrosis factor (TNF)-alpha in 28 studies, IL-10 in 20 studies, IL-8 in 17 studies, C-reactive protein in 14 studies, IL-4 in 10 studies, IL-12 in seven studies, monocyte chemoattractant protein (MCP)-1 in 6 studies, TNF-receptor 2 (TNF-R2) in four studies and granulocyte-macrophage colony-stimulating factor (GM-CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon-gamma, IL-1 beta, IL-2, IL-1 receptor antagonist (IL-1RA), transforming growth factor (TGF)-beta 1, G-CSF, C-C motif chemokine 11, TGF-alpha and SUDs. Conclusions People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL-4, IL-6, IL-8, IL-10, IL-12, TNF-alpha, C-reactive protein, MCP-1, TNF-R2 and GM-CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.