The objectives of the current study were to evaluate the therapeutic effect of dioctahedral smectite (smectite) against calf diarrhea caused by pathogenic E. coli and/or Salmonella typhimurium. In this study, 20 calves (aged 2~3 months) with diarrhea were used for evaluation of the efficacy of smectite on calf diarrhea with 20% smectite suspension in PBS. Calves received 10 ml smectite suspension three times per day after feeding, and fecal samples were collected at the gate of treatment and on the first, second, third, fourth, and fifth day after administration. On the fifth day after treatment with smectite suspension, the diarrhea index showed a significant decrease in the treated group, compared to the control group (P<0.001). The number of pathogenic E. coli in feces of the treated group was significantly decreased, compared to each control group from the second day after treatment (P<0.001), and that of Salmonella typhimurium was significantly decreased from the first day after treatment (P<0.05). According to the results of the current study, 20% smectite suspension had a therapeutic effect on diarrhea caused by E. coli and/or Salmonella in calves.