A systematic review and meta-analysis was conducted in six databases from 1948 to 2015 to assess the antioxidant activity of astaxanthin in humans. Nine randomized controlled trials were included in the systematic review. Results of meta-analysis revealed a borderline significant antioxidant effect of astaxanthin between the intervention and control groups, with a malondialdehyde-lowering effect for lipid peroxidation (p = 0.050). However, the data included here are insufficient. When compared with the baseline in intervention groups, the meta-analysis suggested that astaxanthin supplements significantly decreased plasma malondialdehyde {Standard mean difference (SMD) −1.32 μmol/L [95% CI −1.92, −0.72]; p < 0.0001} and isoprostane (SMD −3.10 ng/mL [95% CI −4.69, −1.51]; p < 0.0001). However, they increased superoxide dismutase (SMD 1.57 U/mL [95% CI 0.57, 2.56]; p = 0.002) and total antioxidant capacity (SMD 0.77 mmol 95% CI [0.12, 1.43]; p = 0.018). For dosage subgroup analysis, high dose (≥20 mg/day) of astaxanthin showed significant antioxidant effect (on total antioxidant capacity, isoprostane, and superoxide dismutase, p < 0.05). However, low dose (<20 mg/day) showed no significant effect (p > 0.05). Further duration subgroup analysis indicated that astaxanthin showed antioxidant effect after a 3-week intervention (p < 0.001), whereas this effect was not observed after a 12-week or 3-month intervention (on isoprostane and superoxide dismutase, p > 0.05). This review suggested that the antioxidant effect of astaxanthin on humans is unclear.