The high cost of protein and energy sources in the poultry diet, especially during the last three years due to climate changes and the COVID-19 pandemic around the world, has become a high challenge to poultry producers. Distillers dried grains with solubles (DDGS) have shown potential as an alternative source for both protein and energy. The experiment was conducted in the summer of 2021 to investigate the effect of dietary inclusion of DDGS in broiler diets on performance, digestibility, immune status, and both ileal histometrics and microbiota. A total of 600 un-sexed one-day-old Ross 308 broiler chicks were randomly distributed into four groups as follows; control, fed a corn-soy diet, other groups were fed diets inclusion with 10, 20, and 30 % DDGS replaced for corn and soybean meal. Results showed that the inclusion of DDGS up to 20 % had non-significant (p< 0.05) effects on performance, carcass traits, and immunological parameters compared with control group. Adverse effects were recorded with 30% DDGS. Body weight gain, digestibility coefficient of crude protein, and production efficiency factor decreased, but feed conversion ratio, mortality rate, and E. coli counts of ileum were deteriorated with 30% DDGS inclusion. In conclusion, the replacement of dietary corn and soybean meal with DDGS at 10 and 20 % had no significant effects on performance, lipid profile, nutrient digestibility, immunological traits, and ileum development.