Objectives The effects of preventing and treating diarrhea in weaned piglets were improved to reduce the incidence of diarrhea, improve gut microbiota, and promote healthy growth of weaned piglets. Methods Sixty weaned piglets aged 21 days without diarrhea, in good physical health, in good mental state, and weighing (6.46±0.58) kg in a large-scale farm in Fengning, Hebei Province were selected and randomly divided into an experimental group and a control group, with 5 replicates in each group and 6 pigs in each replicate according to a single factor experimental design. The weaned piglets in the control group were fed with basic feed, while the weaned piglets in the experimental group were fed with 0.2% compound probiotic preparation (Bacillus subtilis∶Lactic acid bacteria=1∶1) added in the basic feed, and the experiment lasted 15 days. The indexes of growth performance, the incidence of diarrhea, and the content of gut microbiota in piglets were measured. Results The end weight, average daily gain weight, and average daily feed intake of weaned piglets in the experimental group was significantly higher than that in the control group, while the feed to weight ratio in the experimental group was significantly lower than that in the control group. The diarrhea rate of weaned piglets in the experimental group was significantly lower than that in the control group, and the diarrhea rate of weaned piglets in the experimental group decreased by 74.15%. The content of E.coli in the feces of weaned piglets in the experimental group significantly decreased by 57.62%, while the content of Lactobacillus significantly increased by 42.91% compared with that in the control group. Conclusions The combination of Bacillus subtilis and lactobacilli can effectively improve the growth performance of weaned piglets, reduce the incidence of diarrhea, increase the content of lactobacilli in the intestine to improve the gut microbiota.