Background: To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions. Methods: The main aim of this study was to develop a high-performance liquid chromatography method – photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions. The α-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium, based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl, 2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals, were estimated and compared. Results: Among the tested compounds, the content of hesperidin (13.386–68.235 mg/g) was the highest and that of hesperitin (0.045–0.277 mg/g) was the lowest. In comparing different sources of Citri Reticulatae Pericarpium, the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong (0.824–0.851 mg/g) and Sichuan (1.069–1.204 mg/g) provinces of China were lower than in other provinces. In contrast, nobiletin (8.429–12.237 mg/g) and tangeretin (3.947–4.613 mg/g) were most abundant in Guangdong sources of Citri Reticulatae Pericarpium, followed by samples from Sichuan Province (nobiletin: 6.761–7.658 mg/g; tangeretin: 3.422–3.933 mg/g). Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity, and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium. Conclusion: This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions, which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.