ABSTRACT This experiment was conducted to evaluate the supplemental effects of a novel protease produced from Bacillus subtilis in low crude protein (CP) corn distiller dried grain with solubles (cDDGS) based diets on growth performance, carcass attributes, nutrients digestibility, blood chemistry, and intestinal histomorphometry of broiler chickens. One hundred and sixty, one-day-old chicks were randomly allotted to one of 4 dietary treatments. Each dietary treatment had four replicates, with 10 birds in each replicate. Two basal diets were formulated for both starter (1-21d) and finisher (22-35d) phase; (PC) a corn soybean meal based diet as per standard recommendations of Ross 308; (NC) 5% cDGGS with 5% reduction in CP with concomitant reduction in essential amino acids (EAAs) compared with PC. The negative control diet was further subdivided into 3 parts. One part was without enzyme supplementation, while the other two parts were supplemented with a novel protease (PROT1) and a commercial protease (PROT2), respectively. The same procedure was adopted for finisher diets. A digestibility assay (32-35d) was carried out using acid insoluble ash (AIA), an external digestibility marker. At the end of 35d, ileal digesta were collected from four birds per experimental unit for nutrient digestibility measurement. Tissue samples of duodenum, jejunum, and ileum were collected for villus height, villus width, crypt depth, and crypt width. Body weight gain (BWG) and feed:gain were improved (p<0.05) with protease supplementation. No effect was observed on carcass parameters. However, CP digestibility, apparent digestibility coefficient for nitrogen (ADCn), nitrogen retention (N ret ), and apparent ileal amino acid digestibility (AIAAD) were improved (p<0.05). However, there was no effect on apparent metabolizable energy (AME) and apparent metabolizable energy corrected for nitrogen (AMEn), blood glucose, total protein and cholesterol (p>0.05) and intestinal integrity (p>0.05). It was concluded that protease enzyme can improve nitrogen and CP digestibility, resulting in improved amino acids availability in low protein diets.