The aim of this experiment was to evaluate the effects of bioactive peptides derived from sesame meal (BPSM) compared with mannan-oligosaccharides (MOS) as a prebiotic supplementation and avilamycin (as an antibiotic) on the productive performance, internal organs, gut microbial population, and intestinal morphology in broiler chickens. A total of 300 one-day- old broiler chicks were randomly allocated into 6 treatments with 5 replicates per treatment and 10 birds per replicate. The experimental treatments were a control diet or control diet supplemented with 50, 100 or 150 (mg/kg) BPSM or MOS (2 g/kg) and avilamycin (10 mg/kg). Growth performance traits, including daily weight gain, food intake and food conversion ratio (FCR) were recorded. At the end of the study, carcass characteristics, gut microbiot, and intestinal morphometric indices were determined. The results indicated that weight gain increased (P<0.05) in birds received MOS and 100 mg/kg BPSM on days 1-11 and 1-32, respectively. The dietary treatments did not affect food consumption in broilers. However, FCR improved in broiler chickens fed 100 mg/kg BPSM supplement (P<0.05). Inclusion of BPSM, MOS or antibiotic had no effect on the relative weight or length of internal organs compared to control group, except for gizzard weight on day 32. The relative weight of gizzard was significantly lower for MOS treatment than the control group (P<0.05). Addition of antibiotic and 100 mg/kg BPSM supplementation increased the caecum population of Lactobacilli in broiler chickens (P<0.05). Besides, diets supplemented with antibiotic, MOS or all graded levels of BPSM decreased the viable cell count of Escherichia coli in caecum segment of broiler chickens (P<0.05). In the intestinal mrphometric indices, the villus length was greater in antibiotic, MOS, 100 or 150 mg/kg BPSM compared with control diet (P<0.05). In addition, the birds fed diets supplemented with MOS had a greater crypt depth (P<0.05). In conclusion, the positive effect of BPSM supplementation on the performance, gut microbiota, and intestinal morphology was clearly evident for broiler chickens.