Mycotoxins are the primary contaminants in food that have a significant impact on global food safety and security. Cold atmospheric plasma (CAP) has demonstrated significant potential in reducing mycotoxins among innovative technologies. This study aimed to assess the effectiveness of a surface dielectric barrier discharge (SDBD) CAP system in reducing aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), G2 (AFG2), and ochratoxin A (OTA). The distinctive feature of the device here used was the ability to operate at two different powers, resulting in two different plasma reactive species ambients: ozone (O3) and nitrogen oxides (NOx) regimes. CAP treatments exhibited a significant reduction of all investigated pure mycotoxins, which was regime, molecule chemical structure, distance from the source and time-dependent. In particular, O3 regime was more effective (AFB1 and AFG1 99%, AFB2 and AFG2 60%, OTA 70% reduction, respectively, at 60 min, 4 cm distance from the plasma source). As low-moisture foods pistachio kernels (Pistacia vera L. seeds) were selected to evaluate the matrix effect. As expected, the mycotoxins were reduced to a much lesser extent than pure molecules. Worthy of note was the 23% reduction of OTA. To our best knowledge, this is the first investigation about OTA degradation in pistachio food matrix by cold plasma. It should also be noted that the pistachios have been artificially contaminated with spots of a mixture of mycotoxins, to best represent a probable real contamination.