Microplastic (MP) pollution is a pressing issue for both environmental health and the safety of human food sources. This study provides a comprehensive analysis of the effects of MPs on Mediterranean mussels (Mytilus galloprovincialis, Lamarck 1819), focusing on the food safety risks associated with MP and cadmium (Cd) exposure in these organisms intended for consumption. The retention of different polymer types of MPs in mussels was specifically evaluated, and the influence of Cd on MP retention across these polymers was investigated. Mussels were exposed to polystyrene (PS), polypropylene (PP), and polyethylene terephthalate (PET) MPs individually and in combination with the toxic metal Cd for a duration of 7 days. Antioxidant enzymes, oxidative stress parameters, and digestive system enzyme activities, selected as biomarkers for Cd and MPs pollution, were assessed. Furthermore, human consumption risk evaluations and limits regarding mussel intake were analysed in terms of food safety. The results suggest that exposure to Cd, MPs, or their combination induces oxidative stress, tissue damage, and neurotoxicity. Alterations in digestive enzyme activities could impact the mussels' energy acquisition from food and their capacity to conserve energy reserves. The estimated daily intake (EDI), provisional tolerable weekly intake (PTWI), target hazard quotient (THQ), and target cancer risk (TCR) levels for all groups surpassed established limits, implying a significant health risk for humans consuming these products. These results underscore the potential health risks for humans associated with consuming mussels exposed to Cd and/or MPs and provide valuable data for monitoring pollution levels and ecological risks in aquatic organisms. Additionally, our findings reveal that the retention of Cd in mussel tissues varies significantly after exposure, with combinations of PET and Cd showing lower levels of Cd accumulation compared to other groups, suggesting a differential interaction that influences Cd retention.