Bothus podas (wide-eyed flounder) is a benthic flatfish likely exposed to microplastic (MP) pollution. We investigated MP ingestion and associated physiological effects in wild B. podas collected from Mallorca (Balearic Islands), Spain. Markers of oxidative stress, detoxification, and immunity were quantified in intestinal, hepatic, and splenic tissues. MPs were observed in the gastrointestinal tracts of 87.5% of the 24 specimens analyzed, with an average of 3.8 ± 0.6 items per fish. Fiber-type MPs predominated in both the gastrointestinal tract (69.6%) and sediment samples (97%). Additionally, micro-Fourier transform infrared spectroscopy analysis confirmed that the majority of ingested MPs were composed of polyethylene, polypropylene, and polyester. Fish were categorized into low (B. podas. Overall, ingestion of environmentally relevant MP levels elicited detoxification and inflammatory responses without significant increases in MDA, an indicator of oxidative damage, highlighting the physiological stress imposed by plastic pollution on benthic fish.