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Background Caring the eye from oxidative stress is very important in preventing the age-related macular degeneration (AMD), which is difficult to recover it once damaged. Particularly, the development of therapeutic anti-dry-AMD agent in a non-invasive manner is still on the horizon. Purpose In the present study, we examined effect of gypenoside (Gyp) LXXV against dry-AMD in vitro and in vivo, to develop non-invasive anti-AMD agents based on a natural compound with anti-oxidative and anti-inflammatory activity. Study design Gyp LXXV, a single ginseng ginsenoside compound, is orally administered to adult rabbits and mice that the dry-AMD was induced by asodium iodate or a light irradiation, respectively. The in vitro assay was performed using the retinal cells (ARPE-19) and macrophage cells (HMC-3). Methods To evaluate anti-oxidative capability and anti-inflammable efficacy of Gyp LXXV in retinal pigment epithelial (RPE) cells, real time PCR was employed using ARPE-19 cells and HMC-3 cells. To validate physiological effects of Gyp LXXV on dry-AMD, thickness measurement of RPE, electroretinogram (ERG), optical coherence tomography (OCT), and fundus examination were employed in either light irradiation- or sodium iodate-induced animal model. Results It exhibited substantial alleviation of damaged retinal RPE tissues, via lowering the structural damage, the reactive oxygen species (ROS) level, and inflammatory cytokines in a dose-dependent manner, without showing any side effects. In addition, ROS-induced human adult RPE cells were treated with Gyp LXXV showed a protective effect against the ROS, confirming an excellent antioxidant efficacy with no potential cytotoxicity. Conclusion Our findings indicate that the oral route of Gyp LXXV exerts a potential therapeutic effect on dry-AMD. This work could guide the new therapeutic pathway of a phytochemical drug-based non-invasive treatment for dry-AMD in future clinical treatments.