Enterotoxigenic (ETEC) is a major pathogen causing diarrhea in weaned piglets, and oral administration of probiotics has become an important strategy for preventing and treating ETEC-induced diarrhea. The aim of this study was to investigate the protective effect of two probiotics, and , on ETEC-induced injury in piglets. Twenty-four piglets were randomly divided into control (CON) group (fed with a basal diet and treated with sterile saline), ETEC group (fed with the basal diet and treated with ETEC), LP-ETEC group (fed with the basal diet and treated with ETEC and . ) and LB-ETEC group (fed with the basal diet and treated with ETEC and ), with 6 piglets in each group. The experiment lasted for 21 days. The results indicated that both probiotics were able to inhibit the ETEC-induced reduction in daily weight gain of piglets and prevent the damage to jejunum. . significantly increased daily weight gain ( = 0.012), while . showed a similar trend ( = 0.063). Serum metabolomic analysis showed that both probiotics significantly increased some beneficial metabolites including phosphatidylethanolamine, monoacylglyceride, cholic acid and rhodoxanthin ( < 0.05). Transcriptome sequencing indicated that and may alleviate piglet diarrhea by regulating genes including and . According to 16s rRNA sequencing, both probiotics were able to maintain the normal microbial community of the gut. In summary, and can protect piglets from ETEC-induced damage and promote healthy growth of piglets by regulating metabolites and gene expression.