The objective of the present study was to determine the therapeutic effectiveness of orally administered sepiolite on neonatal calf with diarrhea. The study was conducted on fifty 1-30 days old public owned calves (40 animals for experiment and 10 animals for control groups), in Afyonkarahisar region, Turkey. Sepiolite was administered orally to all animals in the experiment group for 30 days, once daily at a rate equal to 2% of their total food intake weight. All studied animals were examined for their clinical, hematological, immunological and blood biochemical parameters, in addition to native examination of feces for Eimeria, Cryptosporidia, Giarda protozoa; rota and corona viruses and E.coli using SRID kits before and after sepiolite intake on days 1, 2, 3 and weeks 1 and 2. The treatment with sepiolite had a significant effect on the body weight and the treatment of diarrhea. No toxic effects were observed. The data obtained from this study indicate that oral intake of sepiolite in calves with diarrhea might contribute to the prevention of economic losses due to diarrhea.