Medical treatment has been shifted to being more prophylactic as a recent trend. Postgenomic research has unveiled the fact that nutritional intervention has been strongly associated with genetic expressions, which are responsible for a variety of biological functions. Based on these findings, the prophylactic effects of dietary supplement and nutrient have been enthusiastically investigated. Preventing or retarding the onset of diseases has become a more attractive and cost effective strategy in the medical arena. Among other approaches to prevent diseases, antioxidants, which are found in many phytochemicals, have received much attention. However, most natural antioxidants such as alpha-tocopherol, ascorbic acid and others are biologically unstable, poorly soluble in water, and poorly distributed to target sites. Because of these shortcomings further prophylactic applications of dietary supplements have stagnated. This is partially due to a lack of basic awareness of drug delivery system for dietary supplements and nutrients. In this article, we strongly advocate serious consideration of the bioavailability of dietary supplements. Currently, there are some challenging works to improve their bioavailability using delivery systems such as liposomal formulations. We will discuss the target molecules of dietary supplements for prevention of diseases and also introduce the pioneering works of delivery systems for dietary supplements to promote their therapeutic value.