Microplastic (MP) pollution is a major global environmental issue, especially in aquatic ecosystems. Despite its vastness and strong currents, the marine environment is highly vulnerable to MP contamination. Microplastics vary widely in chemical composition and size: larger fragments can be ingested by vertebrates that mistake them for food, while smaller particles, down to the micro- and nanoscale, can spread throughout aquatic food webs. Marine mussels, such as Mytilus galloprovincialis, are particularly susceptible because they are filter feeders and continuously process large volumes of water. This species is widely used in environmental biomonitoring due to its broad distribution and commercial importance. However, its role as a common food source also makes it a potential vehicle for transferring microplastics, along with associated chemicals and pathogens, to humans. This study investigated the cytotoxic effects of a 48-hour exposure to 5 μm polystyrene microplastics at two concentrations (0.5 and 1 μg/mL). Histological analyses confirmed the presence of MPs in mussel tissues and revealed significant structural alterations in the gills and mantle, with the latter being particularly relevant as it contains the gonads and represents the main edible portion. Morphological observations showed dose-dependent damage to gills, ovaries, and testes. Exposure caused cellular disorganization, especially in spermatic cysts, and progressive oocyte degeneration. Hypertrophic mucous cells appeared in both male and female gonads, indicating a stress response. This condition was supported by redox imbalance and increased levels of stress-related proteins, including HSP70 and p53. Importantly, MP-induced stress altered sperm chromatin organization, making it more susceptible to DNase digestion. Overall, the findings demonstrate that microplastics disrupt tissue organization, impair reproductive processes, and compromise mussel health and quality, posing ecological risks and potential threats to human consumers.