In recent years, there has been an increase in the reporting of plastic pollution in the marine environment and its effects on marine animals, especially bony fish. However, the prevalence and effect, particularly concerning biomarkers of oxidative stress, in elasmobranchs remain underreported and unknown. In this study, microplastics were observed in two elasmobranch species from the Balearic Islands: the small-spotted catshark (Scyliorhinus canicula) with an average of 4.38 ± 1.77 items per individual, and the blackmouth catshark (Galeus melastomus) with an average of 8.31 ± 2.46 items per individual. Moreover, for the first time, antioxidant and pro-inflammatory responses were determined in the digestive tract of individuals of both species. Specifically, the activation of antioxidant defences, mainly superoxide dismutase activity and glutathione levels, was observed, while the pro-inflammatory marker myeloperoxidase activity was also greater in individuals with a high abundance of microplastic items. Additionally, a significant increase in glutathione S-transferase activity in catsharks with high microplastic ingestion was evidenced, suggesting that the detoxification process was activated. Overall, the results of this study highlight that both catshark species are ingesting microplastics, which, in turn, are causing physiological effects at a cellular level. Considering this, continued monitoring of these species should include the presence of microplastics, and the results from this study can serve as baseline data for future research.