Myopia progression is driven by abnormal signaling pathways, particularly the PI3K/AKT pathway. Using a lens-induced myopia model in guinea pigs, we administered the PI3K/AKT inhibitor LY294002 via intravitreal injection and performed quantitative proteomic analysis with data-independent acquisition mass spectrometry. This study provides retinal proteomic data from normal, myopic, and drug-treated guinea pigs. It also establishes the first comprehensive retinal proteome database for guinea pig myopia, offering insights into myopia development and the role of the PI3K/AKT pathway in its progression.