Deoxynivalenol (DON) and zearalenone (ZEN) contaminated maize was hydrothermally treated in the presence of sodium metabisulphite (SBS), methylamine and calcium hydroxide (Ca(OH)2) and included into diets for female piglets to evaluate effects on performance, organ weights, development of hyperestrogenism, serum biochemical parameters, stimulation of peripheral blood mononuclear cells and toxin residues in serum. For this purpose, both uncontaminated maize (CON) and Fusarium toxin-contaminated maize (FUS) were included into diets either untreated (-) or treated (+) according to a 2 by 2-factorial design. One-hundred female weaned piglets were assigned to one of the four treatment groups (n = 25) CON-, CON+, FUS- and FUS+ with DON/ZEN concentrations of 0.43/0.03, 0.04/0.0, 3.67/0.32 and 0.36/0.08 mg per kg diet, respectively. After a feeding period of 27 days, 20 piglets (n = 5) were slaughtered. Performance parameters such as feed intake, live weight gain and feed-to-gain ratio remained unaffected by the treatments. Uterus weights were significantly reduced in group FUS+ compared to FUS- (p = 0.028), while visceral organ weights were not influenced. Vulva width in relation to body weight was highest in group FUS- at the end of the trial, while hydrothermal treatment significantly reduced the parameter (p < 0.01). The highest toxin and toxin metabolite concentrations in serum were detected in group FUS-, whereas ingestion of diet FUS+ reduced the concentrations to the level of the control groups. Serum biochemical and haematological parameters were mainly within the given reference ranges and showed no treatment-related alterations. Stimulation of peripheral blood mononuclear cells was not affected. An effective detoxification of maize by hydrothermal treatment in the presence of SBS, methylamine and Ca(OH)2 could be demonstrated by means of serum toxin analyses. No undesired side effects of the treated-feed stuff or the chemicals themselves on the health of piglets were detected.