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Simple Summary: The biological characteristics of E. faecium R1 and the effect of dietary supplementation with E. faecium R1 on the growth performance of weaned piglets were studied. The results showed that E. faecium R1 had the characteristics of effective bacteriostatic activity, acid resistance, bile salt resistance, and high-temperature resistance. Dietary supplementation with E. faecium R1 (6.5 × 106 CFU/g) improved intestinal function of weaning piglets by decreasing diarrhea incidence. Further research found that dietary supplementation with E. faecium R1 (6.5 × 106 CFU/g) attenuated intestinal and liver injury in piglets challenged by lipopolysaccharide. In this study, a strain of E. faecium R1 with effective bacteriostatic activity, acid resistance, bile salt resistance, high-temperature resistance was screened. To study the effect of E. faecium R1 on lipopolysaccharide (LPS)-induced intestinal and liver injury in piglets, twenty-four weaned female piglets were randomly assigned into one of three groups (8 piglets per group). Piglets in the control group and LPS group were fed a basal diet, piglets in the E. faecium group were fed the basal diet supplemented with E. faecium R1 (6.5 × 106 CFU/g). On day 21 of the trial, piglets in the LPS group and E. faecium group were intraperitoneally administered LPS (100 μg/kg), piglets in the control group were administered the same volume of saline. Subsequently, blood samples were collected at 3 h, and intestinal, liver, and pancreas samples were collected at 6 h. Results showed that E. faecium R1 supplementation significantly decreased the diarrhea rate and feed to gain ratio, and dramatically reduced LPS-induced intestinal and liver injury in piglets. Compared with the LPS group, E. faecium R1 supplementation significantly increased the content of glucagon in plasma and IL-1β in the liver, and the mRNA levels of villin in jejunum and ileum and Bcl-xL and pBD-L in the ileum, and significantly decreased the contents of prostaglandin 2 and malondialdehyde in the liver and the activities of myeloperoxidase and aspartate aminotransferase in plasma in piglets. Moreover, E. faecium R1 improved the pancreatic antioxidant capacity in piglets, which was indicated by a significant increase in catalase activity and a decrease in total nitric oxide synthase activity. In summary, dietary supplementation with E. faecium R1 alleviates intestinal and liver injury in LPS-challenged piglets. [ABSTRACT FROM AUTHOR]