Synbiotics have been used as biotherapeutic supplements for prevention of new-born calf gastrointestinal disorders. Present study was conducted to evaluate the impact of fructo-oligosaccharide, mannan-oligosaccharide and inulin along with Lactobacillus plantarum CRD-7 and Lactobacillus acidophilus NCDC15 on the nutrient digestibility, growth performance and faecal microbial population of pre-ruminant buffalo calves. Twenty-four Murrah calves (5 days old) were randomly assigned to four groups of six calves in each using randomized block design. Calves in Group I (control) received only a basic diet of milk, calf starter and berseem with no additives. Calves in Group II (SYN1) were fed 6 g fructo-oligosaccharide (FOS) + Lactobacillus plantarum CRD-7 (100 ml). Calves in Group III (SYN2) were fed 9 g inulin + L. plantarum CRD-7 (50 ml), while calves in Group IV (SYN3) received 4 g MOS + L. acidophilus NCDC15 (200 ml) as fermented milk having 108 CFU/ml/calf/day in addition to the basal diet. The results revealed that digestibility of dry matter, crude protein, ether extract and average daily gain were all higher (P < 0.05) in SYN1 as compared to control group. The antioxidant enzyme activity, humoral and cell mediated immunity performed well in SYN1, SYN2 and SYN3 as compared to control. Diarrhoea and faecal scouring were lower (P < 0.05) in all supplemented groups than control. Faecal Lactobacilli and Bifidobacterium counts were also higher in SYN1 group followed by SYN2 and SYN3. Faecal ammonia, lactate, pH, and volatile fatty acids level were increased in SYN1 supplemented groups. The synbiotic combination of 6 g FOS + L. plantarum CRD-7 had better response on digestibility, average daily gain, antioxidant enzymes, immune response, faecal microbiota and metabolites and also reduce the faecal score and diarrhoea incidence. Therefore, supplementation of 6 g FOS + L. plantarum CRD-7 can be advised for general use in order to promote long-term animal production.