We evaluated the efficacy and safety of stir-fried white pepper in the treatment of infant and children diarrhea. This was a randomized trial conducted in the pediatric emergency department of the hospital affiliated to Jining Medical College. One hundred seventy four patients were selected from outpatients from 2011 to 2012. Participants were randomly assigned to treatment with stir-fried white pepper (n = 88) or montmorillonite powder (n = 86). The proportions of chronic diarrhea patients (n = 52) showing success of treatment were similar for both groups. There were great differences between the two groups in acute diarrhea (n = 62) and persistent diarrhea (n = 60), and the cure rate of stir-fried white pepper was higher than montmorillonite powder in both groups. The prescription of stir-fried white pepper significantly decreased the frequency of diarrhea in infants and children under 2.5 years with diarrhea compared to treatment with montmorillonite powder, especially for the patients with acute diarrhea or persistent diarrhea.