<p>Photoreceptors require a finely regulated balance of oxygen, nutrients, and waste removal to sustain visual function. In inherited retinopathies like rhodopsin (RHO)-associated retinitis pigmentosa (RP), disruption in retinal homeostasis leads to neurodegeneration. The most common mutation in RHO, P23H, causes protein misfolding, endoplasmic reticulum (ER) stress, and activation of inflammatory and oxidative stress pathways, ultimately leading to photoreceptor death. Upregulation of the NLRP3 inflammasome and NF-κB signaling in RHO mutant models, highlight inflammation as a key contributor to disease progression, yet targeted therapies remain limited. G protein-coupled receptor (GPCR) signaling is a crucial regulator of retinal homeostasis. We identified galanin receptor 3 (GALR3), a GPCR expressed in retinal cells, as a mediator of photoreceptor degeneration. In the <i>Rho</i>^P23H/+ mouse model, GALR3 expression was upregulated in response to the mutation-induced chronic stress. Both genetic ablation and pharmacological inhibition of GALR3 with the selective antagonist SNAP-37,889 attenuated photoreceptor loss and improved retinal survival. Mechanistically, GALR3 inhibition suppressed pro-inflammatory signaling, promoted anti-inflammatory responses, and activated antioxidant defense pathways. These findings reveal GALR3 as a critical mediator of inflammatory and oxidative stress responses in RHO P23H-associated RP, and its inhibition offers a promising therapeutic strategy to slow retinal degeneration and preserve vision in inherited retinopathies.</p>