Optimizing gut health has a large impact on nutrient digestibility and bioavailability, and super-dosing feed enzymes may be one solution to achieve this. A 42-day grow-out trial was conducted using 192 Ross 308 broilers to determine if super-dosing Natuzyme at 0 g/t, 350 g/t, 700 g/t, and 1000 g/t dose rates could improve the gut morphology, alter the cecal microbial profile, enhance bone mineralization, and improve nutrient digestibility of a wheat–corn–soybean diet (six replicates per treatment, eight birds per pen). One bird per pen was slaughtered at day 42 and gut morphology, cecal microbial profile, and nutrient digestibility were studied. The addition of enzymes tended to increase the villus height in the duodenum, villus height, width, and crypt depth in the jejunum, and villus width and the number of goblet cells in the ileum. Microbial profiling revealed diverse communities; however, they did not significantly differ between treatment groups. Yet, 700 g/t Natuzyme promoted microbes belonging to the genus Romboutsia and Ruminococcus gauvreauii, while 1000 g/t Natuzyme promoted Barnesiella species. The nutrient digestibility demonstrated a significant improvement in all enzyme doses compared to the control. In conclusion, based on the outcomes of this study, a dose rate of 700 g/t Natuzyme is recommended to improve gut morphology and nutrient digestibility, and promote unique microbes which aid in feed efficiency.