Enterotoxigenic Escherichia coli (ETEC), which expresses K88 is the principal microorganism responsible for bacterial diarrhea in pig husbandry, and the indiscriminate use of antibiotics has caused many problems; therefore, antibiotics need to be replaced in order to prevent diarrhea caused by ETEC K88. The objective of this study was to screen excellent lactic acid bacteria (LAB) strains that inhibit ETEC K88 and explore their effects as probiotic supplementation on reproduction, growth performance, diarrheal incidence, and antioxidant capacity of serum in sows and weaned piglets. Three LAB strains, P7, P8, and P15, screened from 295 LAB strains and assigned to Lactobacillus (L.) reuteri, L. amylovorus, and L. johnsonii with high inhibitory activity against ETEC K88 were selected for a study on feeding of sows and weaned piglets. These strains were chosen for their good physiological and biochemical characteristics, excellent exopolysaccharide (EPS) production capacity, hydrophobicity, auto-aggregation ability, survival in gastrointestinal (GI) fluids, lack of hemolytic activity, and broad-spectrum activity against a wide range of microorganisms. The results indicate that LAB strains P7, P8, and P15 had significant effects on improving the reproductive performance of sows and the growth performance of weaned piglets, increasing the activity of antioxidant enzymes and immune indexes in both.