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Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments with 18 replicates per treatment and one pig per replicate. The control group was fed with a basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet had no significant effect on the growth performance of weaned piglets (<i>p</i> > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (<i>p</i> < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (<i>p</i> > 0.05) but increased the content of glutathione in plasma (<i>p</i> < 0.05). Tea residue had no significant effect on the morphology of the jejunum and ileum of piglets (<i>p</i> > 0.05), but it could significantly reduce the content of chloride ions in feces (<i>p</i> < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of <i>TMEM16A</i> and <i>CFTR</i> mRNA in the colon of weaned piglets (<i>p</i> > 0.05). The whole-cell patch clamp recording showed that the<i> TMEM16A</i> and <i>CFTR </i>ion channels could be activated by ionomycin and forskolin, respectively. However, when HT-29 cells transfected with <i>TMEM16A</i> and <i>CFTR</i> channels were treated with tea residue extract, it could significantly inhibit the chloride current of the <i>TMEM16A</i> and <i>CFTR </i>ion channels (<i>p</i> < 0.05).