Persistent diarrhea in children under 24 months old has been a global public health concern, including in Vietnam. Therefore, the authors conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of two Bacillus spore probiotic suspensions, namely LiveSpo CLAUSY containing B. clausii at 2 billion CFU/5 ml ampoule; and LiveSpo DIA30 containing B. subtilis, B. clausii, and B. coagulans at 5 billion CFU/5 ml ampoule, as a supportive treatment for children with persistent diarrhea. Children were randomly allocated into the control (using RO water) and two experimental groups, Clausy (using LiveSpo CLAUSY) and Dia30 (using LiveSpo DIA30), n=30/group. All three groups were treated following the standard protocol at the hospital, supplemented with either placebo or high-dose probiotics up to 4-6 ampoules/day. The results showed that Bacillus spore probiotics helped to shorten the treatment duration by approximately 1-3 days and enhanced treatment effectiveness by 1.3-2.4 folds compared to the control group in reducing the typical diarrhea symptoms, including bowel movements ≥3 times/day, presence of mucus, and diaper stool. Notably, LiveSpo DIA30 exhibited a better efficacy of 10-50% compared to LiveSpo CLAUSY. This is the world’s first clinical study demonstrating the effectiveness of high-dose Bacillus spore probiotics in supporting the treatment of diarrhea symptoms in children with persistent diarrhea.