Deoxynivalenol (DON) is a predisposing factor for necrotic enteritis. This study aimed to investigate the effects of a DON and (CP) challenge on the intestinal morphology, morphometry, oxidative stress, and immune response of broilers. Additionally, we evaluated the potential of a spp. mixture as an approach to mitigate the damage induced by the challenge. One-day-old broiler chickens ( = 252) were divided into seven treatment groups: Control, DON, CP, CP + DON, VL (DON + CP + viable spp. mixture), HIL (DON + CP + heat-inactivated spp. mixture), and LCS (DON + CP + spp. mixture culture supernatant). Macroscopic evaluation of the intestines revealed that the CP + DON group exhibited the highest lesion score, while the VL and HIL groups showed the lowest scores. Microscopically, all spp. treatments mitigated the morphological changes induced by the challenge. DON increased levels of reactive oxygen species (ROS) in the jejunum, and CP increased ROS levels in the jejunum and ileum. Notably, the spp. treatments did not improve the antioxidant defense against CP-induced oxidative stress. In summary, a spp. mixture, whether used as a probiotic, paraprobiotic, or postbiotic, exerted a partially protective effect in mitigating most of the intestinal damage induced by DON and CP challenges.