The sensitivities of the probiotic Leuconostoc mesenteroides B4 to low pH, high salt bile concentrations and various antibiotics were tested, as were the effects of the probiotic and its isomaltooligosaccharide and dextran products on the growth performance and digestive enzymes of orange-spotted grouper Epinephelus coioides. L.mesenteroides B4 was able to survive and grow in pH 2 and 1.0% bile salt. To test the sensitivity of the L. mesenteroides B4, 15 different antibiotics were used. The L.mesenteroides B4 exhibited at least some sensitivity to 11 of the antibiotics tested. Orange-spotted grouper were fed (1) control, (2) isomaltooligosaccharide (0.15%), (3) L. mesenteroides B4 (107 CFU/g), (4) L. mesenteroides B4 (107 CFU/g) + isomaltooligosaccharide (0.15%), or (5) L. mesenteroides B4 (107 CFU/g) + dextran (0.15%) supplemented diets for up to 8 weeks. The mean final weights of the spotted grouper fed with (3) L. mesenteroides B4, (4) L. mesenteroides B4 + isomaltooligosaccharide, and (5) L. mesenteroides B4 + dextran in their diets were significantly higher than that of the control group (p< 0.05). The mean percent weight gains of the spotted grouper fed with (3) L. mesenteroides B4 and (4) isomaltooligosaccharide + L.mesenteroides B4 in their diets were also significantly higher than that of the control group (p < 0.05). The alkaline, neutral, and acid protease activities in the digestive tracts of the fish fed diets with (3) L. mesenteroides B4, (4) L. mesenteroides B4 + isomaltooligosaccharide, and (5) L. mesenteroides B4 + dextran were significantly increased over those in the digestive tracts of the control group fish (p < 0.05). The amylase activities in the digestive tracts of the fish fed with the experimential diets were also significantly increased over those in the digestive tracts of the control group fish (p< 0.05). Furthermore, the lipase activities in the digestive tracts of the fish fed diets with (2) isomaltooligosaccharide and (4) L. mesenteroides B4 + isomaltooligosaccharide were also significantly increased over those in the digestive tracts of the control group fish (p<0.05). Overall, the results of this study indicate that dietary L. mesenteroides B4 and its isomaltooligosaccharide and dextran products could provide an effective method for enhancing the growth performance of orange-spotted grouper.