Pomelo fruits with many different varieties are widely consumed in Vietnam that promote many beneficial health effects. This study provided the discrepancy in morphological structure, chemical properties, and biological properties in four pomelo varieties found in the Mekong Delta, Vietnam including Da Xanh, Nam Roi, Long Co Co, and Thanh Kieu. Da Xanh pomelo has pomelo segments of red-pink colour and high soluble solid content (11.88±0.26oBx). Nam Roi pomelo is recognized by the yellowish colour of the pomelo segment and low soluble solid content (10.62±0.53oBx) while Long Co Co and Thanh Kieu varieties present a pale pink colour. Pomelo segments were observed with high carbohydrate content, low protein and lipid content. Nam Roi pomelo showed the highest total polyphenolic content (TPC) as 2.42±0.01 mg GAE/g dry matter, total flavonoid content (TFC) of 9.57±0.03 mg QE/g dry matter, and vitamin C content of 42.04±1.02 mg/100 g compared to the lowest one (Da Xanh pomelo). Among these varieties, Da Xanh pomelo was favourable in the sensorial aspect of its visual appearance and sweetness while Nam Roi pomelo was observed to have the highest biological activities.