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Simple Summary: In this study, the effects of different levels of wheat inclusion on growth performance and intestinal homeostasis in broilers were evaluated. We first analyzed the effects of dietary wheat ratio on liver function, serum glycolipid profile, and bone turnover, and showed that the dose of wheat in the diets of broilers had no deleterious effects on animal health. We also found that replacing corn with 55% wheat in the diet of broilers increased body weight and feed consumption, with improved intestinal morphology and cecal microbiota composition. These data indicated that the replacement of corn with 55% wheat in the diet promoted the growth performance of 21-day-old broilers via improving intestinal morphology and cecal microbiota. Replacing corn with different levels of wheat in the iso-energy and -protein diet of broilers and the impacts on growth performance and intestinal homeostasis of broilers under the condition of supplying the multienzyme complex were evaluated in this study. A total of 480 10-day-old male broilers were assigned randomly to the low-level wheat group (15% wheat and 35.18% corn), the medium-level wheat group (30% and 22.27%), and the high-level wheat group (55.77% wheat without corn) until 21 d. The different levels of wheat supplementation did not affect hepatic function, serum glycolipid profile, or bone turnover. The replacement of corn with 55% wheat in the diet of broilers increased the body weight at 21 d and feed intake during 10 to 21 d (both p < 0.05), with a comparable feed conversion ratio. Compared with the low-wheat group, the dietary addition of medium or high wheat levels notably increased the ratio of villus height to crypt depth in the duodenum (p < 0.05) and the ileal villus height (p < 0.05). Meanwhile, the supplementation of medium and high wheat in the diet increased the proportion of Bacteroidetes, and a diet with high wheat proportion elevated the content of Firmicutes when compared to the low-level wheat group (both p < 0.05). In addition, the diet containing 30–55% wheat enhanced the anti-inflammatory capability in both the ileum and the serum. These findings suggest that the replacement of corn with 55% wheat in the diet improved the growth performance of 21-day-old broilers, which might be linked to the alteration in intestinal morphology and cecal microbiota. [ABSTRACT FROM AUTHOR]