Objective: A trial was conducted from 11 to 42 d post-hatch to investigate the effectiveness of the supplementation of a multiple-enzyme preparation (Natuzyme Plus) in a wheat-based diet on digesta viscosity, pH and microbial population, villus morphology, feed passage time, nutrient retention, carcass characteristics, blood lipid parameters and growth performance of broiler chickens. Methods: Three hundreds 10-d-old male Ross 308 chicks were allocated to three diets with five replicates of 20 birds per replicate. Dietary treatments were i) a wheat-based diet (W), ii) W+Natuzyme Plus (WN; 500 mg/kg of the diet), and iii) a corn-based diet (C). Results: Birds fed on the C diet had higher average daily gain (ADG, p<0.01), villus height (VH, p<0.01), total tract apparent retention (TTAR) of nitrogen (NT, p<0.01) and ether extract (EE, p<0.01), nitrogen-corrected apparent metabolizable energy ($AME_n$, p<0.05), relative weight (RW, % of body weight) of carcass (p<0.05), blood concentration of triglyceride (TG, on d 40 [p<0.01]), total cholesterol (TC, on d 22 [p<0.05]) and low density lipoprotein (LDL, on d 22 [p<0.01] and 40 [p<0.05]), and also lower feed conversion ratio (FCR, p<0.01), digesta viscosity (p<0.01), count of coliforms (p<0.01) and Escherichia coli (p<0.01) and epithelium thickness (ET, p<0.05) than those fed on the W diet. ADG, FCR, VH, ET, TTAR of NT and EE, RW of carcass, blood concentration of TG (on d 40), TC (on d 22) and LDL (on d 22 and 40) values of the WN diet did not show a significant (p>0.05) difference compared to those of the C diet. Compared to those of the W diet, the WN diet showed the higher count of Lactobacilli and lower count of coliforms (p<0.01) and digesta viscosity (p<0.01). Conclusion: In general, the results of this study showed that Natuzyme Plus supplementation in a wheat-based diet can be appropriate to achieve a comparable growth performance in broiler chickens to those given the C diet probably through improving digesta viscosity, VH, ET, TTAR of NT and EE, $AME_n$, count of Lactobacilli and coliforms.