We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of L-arginine on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6) and TNFα.A systematic search was carried out in PubMed, Embase, Scopus, Cochrane library databases and ISI web of sciences to retrieve the RCTs which examined the effect of L-arginine supplementation on inflammatory biomarkers up to October 2019, with no language and time restriction. Meta-analysis was performed using a random effects model, and I2 index was used to evaluate the heterogeneity.Search yielded 2452 publications. Eleven RCTs were eligible. Results indicated that L-arginine supplementation had no significant effect on inflammatory biomarkers including CRP, IL-6 and TNFα. However, when subgroup analysis was performed, we found that L-arginine supplementation increased CRP levels in subjects with ages >60 years old, participants with baseline circulating CRP levels >3 mg/dl, patients with cancer and when used in enteral formula.Results of the present meta-analysis indicated that L-arginine supplementation increased the circulating concentrations of CRP in subjects with ages >60 years old, subjects with higher levels of CRP, patients with cancer and when used in enteral formula. Therefore, L-arginine should be used with caution in these subjects. However, further well designed, large-scale studies are needed.