Müller glial cells (MGCs) are the principal radial glial cells in the retina, extending across all retinal layers and playing a crucial role in maintaining neuronal homeostasis, regulating metabolism, and participating in damage repair. The response patterns of MGCs differ significantly between species: in lower vertebrates, MGCs possess reprogramming and regenerative abilities, while in mammals, they primarily exhibit reactive gliosis. In diabetic retinopathy, MGCs are activated in a hyperglycemic environment, releasing vascular endothelial growth factors and inflammatory cytokines, which disrupt the blood-retinal barrier, leading to macular edema and participating in the maintenance and repair of foveal morphology. In vitreoretinal interface diseases, MGCs serve as the primary source of the internal limiting membrane and provide mechanical support, contributing to the formation and repair of macular holes and epiretinal membranes. In ischemic retinal diseases, MGCs regulate pathological angiogenesis through pathways such as hypoxia-inducible factor-1α, interacting with microglial cells to exacerbate inflammatory damage. In neurodegenerative diseases such as glaucoma, MGCs regulate cholesterol metabolism and release pro-inflammatory cytokines, creating a neurotoxic microenvironment that promotes retinal ganglion cell death. Recent studies investigating signaling pathways, such as Janus kinase/signal transducer and activator of transcription, have revealed the molecular basis underlying the regenerative potential of MGCs. Although the regenerative capacity of MGCs is limited in mammals, strategies such as gene therapy (e.g., overexpression of neurogenic differentiation factor 1), pharmacological interventions (e.g., fibroblast growth factor 21), and cell reprogramming can partially reactivate their regenerative potential and promote retinal neuron regeneration. Future therapeutic strategies should focus on precisely regulating MGC responses to maximize their neuroprotective effects while suppressing glial scar formation, providing new directions for the prevention and treatment of retinal degenerative diseases.