The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = −0.43, p = 0.06; rhealthy subjects = −0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship.