PURPOSE: Retinal ganglion cells (RGCs) are one the most specialized neural tissues in the body. They transmit (and further process) chemoelectrical information originating in outer retinal layers to the central nervous system. In fact, the optic nerve is composed of RGC axons. Like other neural cells, RGCs will not completely heal after the injury, leading to irreversible vision loss from disorders such as glaucoma that primarily affect these cells. Several methods have been developed to protect or regenerate RGCs during or after the insult has occurred. This study aims to review the most recent clinical, animal and laboratory experiments designed for the regeneration of RGC that apply the stem cell-derived secretome. METHODS: We extracted the studies from Web of Science (ISI), Medline (PubMed), Scopus, Embase, and Google scholar from the first record to the last report registered in 2022, using the following keywords; "secretome" OR "conditioned medium" OR "exosome" OR "extracellular vesicle" AND "stem cell" AND "RGC" OR "optic neuropathy". Any registered clinical trials related to the subject were also extracted from clinicaltrial.gov. All published original studies that express the effect of stem cell secretome on RGC cells in optic neuropathy, whether in vitro, in animal studies, or in clinical trials were included in this survey. RESULTS: In this review, we provided an update on the existing reports, and a brief description of the details applied in the procedure. Compared to cell transplant, applying stem cell-derived secretome has the advantage of minimized immunogenicity yet preserving efficacy via its rich content of growth factors. CONCLUSIONS: Different sources of stem cell secretomes have distinct implications in the management of RGC injury, which is the main subject of the present article.