Evidence suggest soy isoflavones might reduce inflammatory biomarkers, therefore; the objective of this study is to conduct a systematic review and meta-analysis on randomized controlled trials (RCTs) that assessed the effect of soy isoflavones on serum concentration of C-reactive protein (CRP) among postmenopausal women. Literature search was conducted by searching PubMed, Scopus, ISI Web of Science, Cochrane Library, and Clinicaltrials.gov up to January 2020. The mean change from baseline in the CRP concentrations and its SD for both intervention and comparison groups were used to compute the effect size. The summary of the overall effects and heterogeneity was estimated by using the DerSimonian and Laird random effects model. The protocol was registered with PROSPERO (No. CRD42020166053). This article considered 23 articles for systematic review and 19 articles for meta-analysis. The overall effect suggested a non-significant effect of soy isoflavones on serum CRP concentrations (WMD= 0.08 mg/L, 95% CI: -0.08, 0.24; p=0.302) and the overall effect of the combination of soy isoflavones plus soy protein indicated non-significant effect in serum levels of CRP (WMD= -0.02 mg/L 95% CI: -0.12, 0.08; p=0.715). There was no significant change in serum levels of CRP in subgroup analysis based on dose, age, intervention duration, baseline CRP level, sample size, region, quality assessment, publication year, and health status. Dose response analysis revealed no association of higher dose of soy isoflavones with isoflavones effect on CRP levels.