The study analyzed the safety of sodium pentosan polysulfate (PPS) based on 11,471 reports from the FAERS database from the first quarter of 2004 to the first quarter of 2025. The most frequent signals were focused on eye disorders, especially pigmentary maculopathy with an exceptionally high odds ratio (ROR). Extraocular signals such as depression and anxiety have also been identified. Maculopathy signals were prominent in females, while gastrointestinal and urinary adverse effects were observed in males. The median time to onset of adverse events was 1,715 days (based on 297 cases), with a Weibull model showing a decreasing hazard rate over time. The majority of reports (68.1%) were serious. The analysis confirms the long latency of risks, especially of vision-threatening maculopathy, and reveals sex-specific profiles. The findings highlight the need for ophthalmologic screening and monitoring in PPS patients.