The aims of the study were to investigate the toxicity of zearalenone (ZEA) on nutrient availability, genital organs and serum hormones of piglets, and to evaluate the efficacy of modified montmorillonite clay (Calibrin-Z) in preventing ZEA-induced adverse effects. The experiment was conducted for 22 d using 36 piglets weaned at 21 d of age (Landrace × Yorkshire × Duroc, 18 females and 18 males; 8.84 ± 0.21 kg average body weight). Piglets were housed and fed individually for the entire experimental period. Blood samples were taken and piglets were sacrificed at the end of the experiment to obtain organs for physiological assessment. Results showed that treatments had no effect on average daily gain (ADG), average daily feed intake (ADFI), feed efficiency (FE, g gain/g feed) and apparent digestibility of nutrients. Females fed ZEA-contaminated diet without clay showed increase in vulva size, relative weight of genital organs and proliferative changes of the corpus uteri tissues. However, the decreased relative weight of genital organs in males were observed without difference in the testicle size and histological changes. Serum progesterone (PG) and testosterone (Ts) in males and females, and estradiol (E2) in females were significantly decreased by the additional ZEA in feeds. Dietary addition of clay in the ZEA-contaminated (1.05 mg/kg) diet showed a positive protection effect on the nutrient availability of GE and CP, net protein utilization (NPU), relative weight of genital organs in piglets, proliferative changes of the corpus uteri tissues in females, and serum hormones of PG and Ts in males and females, and E2 in females. However, piglets fed the control diet with clay alone at 1 g/kg level had no impact on any of the parameters as compared to the control. It suggested that feeding ZEA at about 1.05 mg/kg can result in a deleterious effect on piglets, which was totally or partly ameliorated by dietary supplementation of modified calcium montmorillonite clay at concentrations between 1 and 4 g/kg diet.