Girdin is a nonreceptor guanine nucleotide exchange factor but functions as a guanine nucleotide exchange factor for the G protein Gαi. It plays a crucial role in regulating cell migration and adhesion, as well as protecting cells from apoptosis. Previous research has demonstrated that Girdin activates Akt through a pathway involving phosphatidylinositol 3-kinase (PI3K) in HeLa cells. Our earlier studies revealed that light-induced activation of the PI3K/Akt pathway in the retina is controlled by G-protein-coupled receptor activation, specifically the rhodopsin-dependent insulin receptor. In our current study, we investigated the localization and interaction of Girdin with the p85α-subunit of PI3K. Our findings indicate that Girdin is present in photoreceptor cells and interacts with the p85α-subunit of PI3K in response to light stimulation. Activation of the PI3K/Akt pathway promotes the survival of photoreceptor cells. These results suggest that Girdin might be a novel factor contributing to the protection of photoreceptors in response to light, potentially offering new insights into neuroprotection for these cells.