Creatine supplements are intended to improve performance, but there are indications that it can overwhelm liver and kidney functions, reduce the quality of life, and increase mortality. Therefore, this is the first systematic review and meta-analysis study that aimed to investigate creatine supplements and their possible renal function side effects. After evaluating 290 non-duplicated studies, 15 were included in the qualitative analysis and 6 in the quantitative analysis. The results of the meta-analysis suggest that creatine supplementation did not significantly alter serum creatinine levels (standardized mean difference = 0.48, 95% confidence interval 0.24-0.73, P = .001, I2 = 22%), and did not alter plasma urea values (standardized mean difference = 1.10, 95% confidence interval 0.34-1.85, P = .004, I2 = 28%). The findings indicate that creatine supplementation does not induce renal damage in the studied amounts and durations.