Durian (Durio zibethinus Murr.) is an energy-dense seasonal tropical fruit grown in Southeast Asia. It is one of the most expensive fruits in the region. It has a creamy texture and a sweet-bitter taste. The unique durian flavour is attributable to the presence of fat, sugar, and volatile compounds such as esters and sulphur-containing compounds such as thioacetals, thioesters, and thiolanes, as well as alcohols. This review shows that durian is also rich in flavonoids (i.e., flavanols, anthocyanins), ascorbic acid, and carotenoids. However, limited studies exist regarding the variation in bioactive and volatile components of different durian varieties from Malaysia, Thailand, and Indonesia. Experimental animal models have shown that durian beneficially reduces blood glucose and cholesterol levels. Durian extract possesses anti-proliferative and probiotics effects in in vitro models. These effects warrant further investigation in human interventional studies for the development of functional food.