To conduct a comparative analysis of layer-by-layer macular thickness, peripapillary retinal nerve fiber layer (pRNFL), and minimum rim width (MRW) between the eyes of patients with prostate cancer undergoing treatment with androgen receptor pathway inhibitors (ARPIs) and those of age- and sex-matched healthy controls, with the aim of assessing the potential effects of ARPIs on retinal structure. In this prospective cross-sectional study, 80 eyes of 80 patients with ARPI-treated metastatic prostate cancer and 80 eyes of 80 age-matched healthy controls were evaluated using Heidelberg Spectralis optical coherence tomography (OCT). Layer-by-layer macular thickness, pRNFL, and MRW were measured and compared between groups. Thickness in most segments of retinal layers and pRNFL, as well as all MRW values, were significantly lower in the ARPI-treated group than in the controls ( < 0.05). No significant differences were observed between groups in terms of age, visual acuity, intraocular pressure, central corneal thickness, or lens status. This study is the first to evaluate layer-by-layer macular thickness in patients with metastatic prostate cancer treated with ARPIs, revealing significant thinning in nearly all macular layers, pRNFL, and MRW. These findings suggest that ARPI therapy may induce neurodegenerative changes in retinal and optic nerve structures. Therefore, further research is warranted to assess the ocular safety of these therapeutic agents.