This study was carried out to investigate the effects of enzyme, probiotic or their combinations on growth response, microbiota and gut histopathological indices of broiler chicken. One hundred and fifty (150) one-day old unsexed Arbor Acre broiler chicks were weighed and randomly allotted to 5 dietary treatments; each diet had 5 replicates of 6 birds each in the study that lasted for 42 days. Treatment 1 consists of the basal diet (negative control; NC): Treatment 2 was NC+0.1% antibiotic (positive control), Treatment 3: NC+0.4% probiotic, Treatment 4: NC+0.1% enzyme and Treatment 5: NC+0.4% probiotic+0.1% enzyme. Performance indices were measured. On day 42, ileal digesta was collected from two birds per replicate for microbial count while about 5 cm of distal ileum was severed for histopathology. The results showed that diets had no significant (p>0.05) effect on the performance of birds at the starter and finisher phases. Total heterotrophic counts of birds fed with basal and probiotic diets were similar but significantly (p<0.05) higher than other diets. The highest Lactobacilli count was recorded in the mixture of probiotic + enzyme diet while least was observed in probiotic (2.58×105 cfu/ml) and enzyme supplemented diets (1.45×105 cfu/ml). Total coliform count of birds fed antibiotic diet was significantly (p<0.05) lower (14.12×105 cfu/ml) than for those on other diets. Total Escherichia coli count was highest in birds fed antibiotic while least was observed in birds fed mixture of probiotics + enzyme diet. Photomicrographs of the ileum of birds fed basal diet showed sloughed mucosa layer and degenerated villi. However birds fed antibiotic, probiotic, enzyme or probiotic+enzyme diets showed normal mucosa layer with normal villi, the lamina proprial showed normal tissues with mild infiltrate. In conclusion, feed supplements used in this study can serve as viable alternatives to antibiotics in broiler nutrition without compromising birds’ health