Introduction. Fatigue is a common symptom, but only a few effective treatments are available. This study was conducted to assess the efficacy and safety of the human placental extract solution, which has been known to have a fatigue recovery effect. Methods. A total of 315 subjects were randomly assigned to three groups: group 1 (with Unicenta solution administration), group 2 (with exclusively human placental extract administration, excluding other ingredients from the Unicenta solution), and the placebo group. Subsequently, solutions were administered for four weeks. Results. The fatigue recovery rate was 71.00% in group 1, 71.72% in group 2, and 44.21% in the placebo group, which show statistically significant differences between the group 1 and the placebo group (P value = 0.0002), and between group 2 and the placebo group (P value = 0.0001). Conclusion. The human placental extract solution was effective in the improvement of fatigue.