This study was intended to assess the effect of graded replacements of corn gluten meal with Brewer’s yeast (Saccharomyces cerevisiae), with and without Bacillus megaterium supplementation, on performance, carcass characteristics, and the gut broilers microflora composition. A total of 720 mixed sex one-day-old broiler chicks (Ross 308) were randomly assigned to six dietary treatment groups (6 replicates each) in a 3 × 2 factorial arrangement, including 3 levels of Brewer’s yeast (BY; 0, 25, and 50%, to replace corn gluten meal; CGM) in the presence (+) or absence (−) of B. megaterium used as probiotic (Pro). The results showed that broilers fed diets containing BY up to 25% had comparable body weight (BWG), feed intake (FI), and feed conversion ratio (FCR) to the birds fed only CGM, over the entire feeding period (days 1–35). Conversely, higher levels of BY (50% replacing CGM) registered the lowest BWG values (P < 0.001) and impaired FCR (P < 0.010), but without effects on FI. The BY diets did not significantly affect the main broiler’s carcass traits. The diets with Pro did not involve modifications on carcass and organs size, but a tendency to increase the gizzard weight (P = 0.094) and to decrease SIL (P = 0.076) was observed. Pro addition also, reduced the cecal pH (P = 0.040) and diminish the total coliforms (P < 0.010), Clostridium spp. (P < 0.0001), and E. coli (P < 0.0001) count, whereas LAB, Bacillus spp., and Enterococcus spp. bacteria were increased (P = 0.022; P < 0.0001, and P < 0.0001, respectively).