The current study aimed to evaluate the effect of replacing soybean and corn with corn distillers dried grains with ith solubles (DDGS) in grower and finisher broiler diets on performance, nutrients digestibility, blood constituents, immune response, as well as intestinal health indications.  A total of three hundred and sixty 21-day-old broiler chicks (Ross 308) were divided into four groups, each group included six replicates of 15 birds each.  The control group (CON) was fed the basal diet, whereas the second (D5), third (D10), and fourth (D15) groups were fed diets with 5%, 10%, and 15% DDGS, respectively at the expense of corn and SBM. Birds fed 5% and 10% DDGS showed an improvement in body weight and feed conversion ratio than those fed 15% DDGS and CON groups.Also, relative economic efficiency records an increase with DDGS treatments. All DDGS levels showed significantly decrease in plasma cholesterol concentration, while increased HDL values compared to the control group. As well, crude protein digestibility is enhanced; while dry matter, ether extract, nitrogen-free extract digestibility, and AMEn were not affected by dietary treatments. Likewise, no variance in carcass characteristics, lymphoid organs (%), and ileal histomorphology were observed by the dietary treatments (p < 0.05). Increased the cecum content of Escherichia coli in birds fed 15% DDGS were observed. According to results observed in this work, it could be concluded that DDGS is a valuable ingredient and might be added in the broiler diet up to 15% without any processing or addition. Also, poultry nutrition experts should investigate the possibility of adding DDGS at higher rates or mixing some suitable bio-additives that might help to improve the nutritional value and increase the utilization of DDGS, as a cheap by-product