This systematic review aimed to synthesize and quantify the results of the studies investigating the changes in fibroblast growth factor-21 (FGF-21) induced by exercise. We searched for studies that did not differentiate between patients and healthy adults but compared them before and after exercise and with and without exercise. For quality assessment, the risk-of-bias assessment tool for nonrandomized studies and the Cochrane risk-of-bias tool were used. A quantitative analysis was performed using the standardized mean difference (SMD) and random-effects model in RevMan 5.4. A total of 94 studies were searched in international electronic databases, and after screening, 10 studies with 376 participants were analyzed. Compared with no exercise, there was a significant increase in the FGF-21 levels from before to after exercise (SMD = 1.05, 95% confidence interval (CI), 0.21 to 1.89). The changes in FGF-21 levels in the exercise group showed a significant difference from the levels in the controls. The results of the random-effects model were as follows: SMD = 1.12; 95% CI, −0.13 to 2.37. While the data on acute exercise were not synthesized in this study, FGF-21 levels generally increased after chronic exercise compared with no exercise.