ObjectiveAccording to the “antioxidants network” theory, the present study was conducted to evaluate the regulation of an antioxidant blend on intestinal redox status and major microbiota of early-weaned piglets. MethodsPiglets from 15 litters were randomly allocated by litter to the control group (suckling normally, fed the basal diet, n = 5), the weaning group (weaned at age 21 d, fed the basal diet, n = 5), and the repair group (weaned at age 21 d, fed the basal diet supplemented with an antioxidant blend, n = 5). The redox status and major microbiota in jejunum and colon tracts of 24-d-old piglets were detected, respectively. ResultsEarly weaning resulted in significant decreases in jejunum and colon antioxidant capacities, Lactobacillus and Bifidobacterium counts, and significant increases in levels of jejunum malondialdehyde, colon hydroxyl radicals, jejunum and colon H2O2, and Escherichia coli counts in piglets. The observed imbalance of the intestinal redox status and microbiota was significantly restored by the antioxidant blend. Interestingly, intestinal selected antioxidative items presented a positive correlation with potential beneficial bacteria and a negative correlation with E. coli. Nevertheless, selected oxidative items and the bacteria presented an inverse relationship in piglets. ConclusionSupplementation of the antioxidant blend effectively restored intestinal redox status and microbiota balance in the porcine intestine in response to early weaning stress, enhancing intestinal health and function of piglets.