A total of 300 one-day-old chicks were divided into five dietary treatments: a positive control (PC), two negative control diets with reduced metabolizable energy (NC1, reduced by 80 kcal/kg diet, and NC2, reduced by 100 kcal/kg diet), and each negative control diet supplemented with lipase at 200 g/ton of diet. Birds fed the PC diet and the NC1 diet supplemented with lipase showed significantly higher body weight (P < 0.05), whereas those fed the NC2 diet had the lowest body weight. The highest digestibility of crude protein (CP) and ether extract was observed in the PC and NC1 plus lipase groups. In addition, the highest glutathione peroxidase levels were recorded in birds fed the NC1 diet, while the lowest malondialdehyde levels were found in the low-energy diets supplemented with lipase, followed by the unsupplemented low-energy diets. Economically, birds reared on the NC1 diet supplemented with lipase achieved the highest economic indices and the lowest feed cost per kilogram of body weight gain, without significant differences compared to the PC group. Overall, supplementation of lipase to reduced-energy diets markedly improved growth performance, nutrient utilization, economic efficiency, and antioxidative status in broilers.