Background: The association between serum C-peptide concentration and prostate cancer remains unexplored. Therefore, we conducted a meta-analysis to assess whether C-peptide serum concentrations are associated with increased prostate cancer risk. Methods: Several databases were searched to identify relevant original research articles published before November 2017. Random-effects models were used to summarize the overall estimate of the multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: Nine observational studies involving 11,796 participants were identified. The findings of the meta-analysis indicated that the association between serum C-peptide concentration and prostate cancer was not significant (OR: 1.15, 95% CI: 0.85-1.54; for highest versus lowest category C-peptide concentrations, P=.376). The associations were inconsistent, as indicated by subgroup analyses. Conclusion: Although our findings provided no support for the hypothesis that serum C-peptide concentration is associated with excess risk of prostate cancer, people must pay attention to this aspect and increase physical activity or modify dietary habits to constrain insulin secretion, which possibly lead to decreased incidence of prostate cancer. Hence, well-designed observational studies involving different ethnic populations are still needed.