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Blue light is the higher-energy region of the visible spectrum. Excessive exposure to blue light is known to induce oxidative stress and is harmful to the eyes. The stems of <i>Dendrobium nobile</i> Lindl. (Orchidaceae), named Jinchaishihu, have long been used in traditional Chinese medicine (TCM) for nourishing yin, clearing heat, and brightening the eyes. The polysaccharide is one of the major components in <i>D. nobile</i>. However, the effect on ocular cells remains unclear. This study aimed to investigate whether the polysaccharide from <i>D. nobile</i> can protect the eyes from blue light-induced injury. A crude (DN-P) and a partially purified polysaccharide (DN-PP) from <i>D. nobile</i> were evaluated for their protective effects on blue light-induced damage in ARPE-19 and 661W cells. The in vivo study investigated the electroretinographic response and the expression of phototransduction-related genes in the retinas of a <i>Drosophila</i> model. The results showed that DN-P and DN-PP could improve blue light-induced damage in ARPE-19 and 661W cells, including cell viability, antioxidant activity, reactive oxygen species (ROS)/superoxide production, and reverse opsin 3 protein expression in a concentration-dependent manner. The in vivo study indicated that DN-P could alleviate eye damage and reverse the expression of phototransduction-related genes, including <i>ninaE</i>, <i>norpA, Gαq</i>, <i>Gβ76C</i>, <i>Gγ30A</i>, <i>TRP</i>, and <i>TRPL</i>, in a dose-dependent manner in blue light-exposed <i>Drosophila</i>. In conclusion, this is the first report demonstrating that <i>D. nobile</i> polysaccharide pretreatment can protect retinal cells and retinal photoreceptors from blue light-induced damage. These results provide supporting evidence for the beneficial potential of <i>D. nobile</i> in preventing blue light-induced eye damage and improving eyesight.