Inflammation is the main cause of several chronic diseases such as diabetes and respiratory diseases. The results of several clinical trials that investigated the effects of soy on inflammatory biomarkers are controversial. This study aimed to evaluate the effect of soy and its isoflavones consumption on inflammatory biomarkers through running a systematic review and meta-analysis. We searched Medline, Scopus, ISI Web of Science, and Google Scholar systematically for clinical trials that evaluated the effects of soy and its isoflavones on tumor necrosis factor α (TNF-α), Interleukin-6 (IL-6), Interleukin-2 (IL-2), Interleukin1-β (IL1-β), and Interferon gamma (IFN-γ) in adults. Overall effects were calculated using A random effects method, and subgroup analyses were conducted to identify probable sources of inter-study heterogeneity. Finally, twenty-eight clinical trials were included. Although soy consumption reduced TNF-α (Hedges’ g = –0•28; 95 % CI –0•49, –0•07), it had no significant effect on IL-6 (Hedges’ g = 0•07, 95 % CI –0•14, 0•28), IL-2 (mean difference (MD) = –1•38 pg/ml; 95 % CI –3•07, 0•31), IL-1β (MD = –0•02 pg/ml; 95 % CI –0•08, 0•03) and IFN-γ (MD = 1685•82 pg/ml; 95 % 22 CI –1604•86, 4976•50). In parallel studies, at dosages ≥100 mg of isoflavones, and in unhealthy subjects, decreased TNF-α level was found after subgroup analysis. The present study indicated that high doses of isoflavones among unhealthy subjects may have useful effects on TNF-α levels. Further studies should be conducted to clarify efficacy of soy consumption on inflammatory biomarkers.