Pycnogenol is a standardized extract from the bark of the French maritime pine. The aim of the present systematic review and meta-analysis was to clarify the effect of Pycnogenol supplementation on C-reactive protein (CRP) concentration. To identify eligible studies in order to find clinical trials which examined the effect of Pycnogenol supplementation on the level of CRP in adult participants, PubMed, Scopus, and Google Scholar were systematically searched until December 2017. Mean of CRP was collected to estimate the effect size of the supplementation. Potential sources of heterogeneity were explored by subgroup analysis. Five trials including 324 participants were included in this meta-analysis. Pooled effect size showed significant effect of Pycnogenol supplementation on CRP (−1.22 mg/dL, 95% confidence interval, −2.43, −0.003; I² = 99%, p_{heterogeneity} < 0.001). When the meta-analysis was subgrouped by dose of Pycnogenol, heterogeneity was attenuated in > 150 mg/d category (I² = 0.0%, p = 0.42). There was significant difference between-subgroup heterogeneity (p < 0.001). Furthermore, no evidence of publication bias for CRP (p = 0.27, Begg's test and p = 0.62, Egger's test) was seen. Present systematic review and meta-analysis suggested Pycnogenol consumption can decrease the level of CRP and have anti-inflammatory effect. So, Pycnogenol as an anti-inflammatory agent might be a priority in interventions. Further studies with large-scale and better design are needed to confirm this result.