Aflatoxin B1 (AFB1), the mainly Aspergillus fungi derived mycotoxin, is well known for its carcinogenic effects on liver and frequently occurs in food supplies, leading to fatal consequences in both farm animals and humans. Poultry, one of the most important segment of agro-industry, has demonstrated to be extremely sensitive to AFB1 intake, which results in chickens' low performance, decreased quality of both eggs and meat and a negative economic feedback. Oxidative stress caused by AFB1 plays a crucial role in chickens' kidney damage by generating lipid peroxidation accompanied by a concomitant increase in the antioxidant enzymes involved in ROS metabolism [NADPH oxidase isoform 4 (NOX4) and its regulatory subunit p47-phox]. The aim of the present work was to investigate the benefits of dietary supplementation, in chickens affected by AFB1 mycotoxicosis, using a new Feed additive (FA) containing a mixture of a tri-octahedral Na-smectite with a ligno-cellulose based materialas an antioxidant adjuvant. Exposure of AFB1 treated chickens with the feed additive induced a significant down-regulation of both NOX4 and p47-phox genes expression levels. This trend was confirmed by their protein expression, demonstrating the great potential of the FA to counteract oxidative stress. To conclude, these results could open new perspectives in the way to feed chickens using eco-friendly dietary supplements able to reduce AFB1-induced mycotoxicosis and to ameliorate poultry performances.