The objective of the current experiment was to evaluate whether hydrogen-rich water (HRW) or lactulose (LAC) could protect against the adverse effects of Fusarium mycotoxins-contaminated diet on the growth performance and antioxidant status in weaning piglets. A total of 24 individually housed female piglets were randomly assigned to receive four treatments for 25 days (six pigs/treatment): uncontaminated basal diet (negative control), mycotoxin-contaminated (MC) diet, MC diet + HRW (MC + HRW) and MC diet + LAC (MC + LAC). The plasma hydrogen levels before and after 2 h hydrogen-free water/HRW administration were detected at day 21, and the liver hydrogen levels were detected at the end of the experiment. Serum hormones related to appetite regulation, and serum and liver oxidant and antioxidant status were also measured at the end of the experiment. Results showed that both HRW and LAC treatments significantly attenuated the reduction of average daily gain (ADG) and average daily feed intake (ADFI) caused by Fusarium mycotoxins. LAC administration increased the hydrogen concentrations in plasma and liver. HRW treated group had higher plasma hydrogen levels than the MC group. Compared with the NC group, the MC group had significantly increased serum peptide YY (PYY) and cholecystokinin (CCK) levels. Interestingly, both HRW and LAC administrations had a lower reduced serum PYY and CKK levels. Most importantly, oral administration of HRW and LAC attenuated the Fusarium mycotoxins-induced oxidative stress. In conclusion, oral administration of hydrogen-rich water or lactulose could both protect against the growth reduction and oxidative damage caused by Fusarium mycotoxins.