Abstract: In this study, the antioxidant potential of Citrus macroptera fruit was compared between its pulp (CMPU) and peel (CMPE). The biochemical effects of an ethanol extract of CMPU were investigated on major organs, including the liver, kidney and pancreas. Male wistar rats (n = 24) were randomly divided into four groups, including Group I (control), Group II (250 mg kg–1), Group III (500 mg kg–1) and Group IV (1000 mg kg–1) and they were administered the extract for 28 days. The CMPE contained higher amounts of total polyphenols (620.91±7.75 mg), flavonoids (508.33±5.49 mg), tannins (585.99±4.46 mg) and protein (4.00±0.14 g) compared to the pulp (291.06±10.14, 145.02±0.36, 526.08±3.32 mg/100 g and 2.89±0.32 g/100 g, respectively). Similarly, CMPE also exhibited higher 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity and Ferric Reducing Antioxidant Power (FRAP) values than CMPU. However, the ascorbic acid content was higher in CMPU (120.83±0.0019 mg/100 g) than CMPE. In vivo studies confirmed that CMPU possessed a significant lipid lowering activity that occurred in a dose dependent manner and that it caused beneficial changes in several other biochemical parameters. Additionally, a significant diminution of lipid peroxidation in liver and kidney tissues was observed. It was concluded that C. macroptera possesses high antioxidant potential and is relatively safe. Its protective effects against various chronic diseases that are associated with oxidative stress should be further investigated.