Ingestion of mycotoxins can result in many problems, including decreased growth rates and immune suppression. The present study aimed to evaluate the impact of the supplementation of a mycotoxin deactivator composed by adsorbent clay minerals; inactivated fermentation extracts of Saccharomyces cerevisiae; and blend of antioxidants, organic acids, and botanicals in diets containing added mycotoxins for nursery pigs on their performance and antioxidant status. Ninety pigs weaned with 24 d of age (7.12 ± 0.68 kg of BW) were used. Pigs were housed in pens of three animals each according to body weight, litter origin, and sex. The dietary treatments consisted of feeding the pigs with a standard control diet as negative control (NC; mycotoxin levels at accepted regulatory Brazilian Ministry of Agriculture standards; deoxynivalenol (DON): <100 μg/kg; zearalenone (ZEA): <20 μg/kg; fumonisins (FB): <1 mg/kg); the standard diet added with mycotoxins to reach a low contamination level is considered as positive low (PCL-; DON: 900 μg/kg; ZEA: 100 μg/kg; FB: 5,000 μg/kg) without deactivator; a positive low added the deactivator at an inclusion rate of 1 kg/ton (PCL+); the standard diet added with mycotoxins to reach a high contamination level is considered as positive high (PCH-; DON: 4,500 μg/kg; ZEA: 500 μg/kg; FB: 18,000 μg/kg) without the deactivator; and a positive high added the deactivator at an inclusion rate of 5 kg/ton (PCH+). Pigs were individually weighed at the beginning and at the end of each phase and feed intake recorded based on daily pen intake during the experiment. On days 7, 19, 34, and 43 post-weaning, blood samples were drawn for antioxidant analyses. Antioxidant enzymes (glutathione peroxidase [GPx] and total superoxide dismutase [TSOD]), vitamins [Vit A, E, and C], and malondialdehyde [MDA]) were evaluated in erythrocyte and plasma samples. Pigs challenged with mycotoxins presented lower performance traits, decrease in the efficiency of central antioxidant systems (↓GPx, ↓TSOD, ↓Vit A, ↓Vit E, and ↓Vit C), and a higher oxidative damage to lipids (↑MDA) when compared with the control and deactivator-associated treatments. Our findings showed that the use of a mycotoxin deactivator can mitigate the negative impacts on performance and oxidative stress when animals are subjected to diets contaminated by different levels of mycotoxins.