One hundred-eighty piglets (Duroc × Landrace × Yorkshire), with an average initial weight of 7.4 kg weaned at 27 ± 1 days of age, were used to evaluate the effects of dietary zinc oxide-montmorillonite hybrid (ZnO-MMT) on growth performance, diarrhea, intestinal mucosal integrity, and digestive enzyme activity. All pigs were allotted to five treatments and fed with the basal diets supplemented with 0, 250, 500, and 750 mg/kg of Zn as ZnO-MMT or 2,000 mg/kg of Zn as ZnO. The results showed that supplementation with 500 or 750 mg/kg of Zn from ZnO-MMT and 2,000 mg/kg of Zn from ZnO improved average daily gain, enhanced average daily feed intake, decreased fecal scores at 4, 8, and 14 days postweaning, reduced intestinal permeability which was evident from the reduced lactulose recovery and urinary lactulose/mannitol ratio, and improved the activities of protease, amylase, lipase, trypsin, and chymotrypsin both in pancreas and small intestinal contents of pigs as compared with the control. Supplemental 250 mg/kg of Zn from ZnO-MMT also decreased fecal scores at 8 and 14 days postweaning, decreased urinary lactulose/mannitol ratio, and improved chymotrypsin activity in pancreas and small intestinal contents as well as protease activity in small intestinal contents compared with control. Moreover, the above indexes of weanling pigs fed with 500 or 750 mg/kg of Zn as ZnO-MMT did not differ from those fed with 2,000 mg/kg of Zn as ZnO. The results demonstrated that supplementation with 500 or 750 mg/kg of Zn from ZnO-MMT was as efficacious as 2,000 mg/kg of Zn from ZnO in improving growth performance, alleviating postweaning diarrhea, and enhancing intestinal mucosal integrity and the digestive enzyme activities in pancreas and small intestinal contents of pigs. The results that feeding lower concentrations of ZnO-MMT to weanling pigs maintained performance will be beneficial for the environment and for sustaining swine production.