Natural products hold great promises for being developed into chemopreventive drugs due to their low toxicity and high accessibility. However, poor oral bioavailability limits the biological effects of many natural products in vivo. This paper reviews the factors that affect the bioavailability of several classes of important chemopreventive natural products including resveratrol, curcumin, berberine, genistein, quercetin, allium compound, and ginsenoside compound K. The up-to-date research data suggested that membrane permeability, solubility, and metabolism are the primary factors that limit the oral bioavailability of these natural products although chemical and microbial stability may also contribute to the problem. An important direction for future investigation is to further optimize the oral bioavailabilities of these natural products and realize their chemopreventive and chemotherapeutic effects in vivo.