This Special Issue presents the latest research findings and existing knowledge regarding the disease prevention effects (including antioxidative, anti-tumor, anti-obesity, anti-diabetes, anti-inflammatory, cardiovascular-protective, skin-protective, and neuroprotective activities) of dietary bioactive compounds. The underlying molecular mechanisms of how these dietary bioactive compounds regulate their health-promoting effects are discussed. The Special Issue includes eleven papers covering the above-mentioned aspects, with six reviews and five research papers. The results of the above-mentioned studies will fill the gap between our knowledge of natural bioactive compounds and their underlying cellular signaling and molecular mechanisms. Further studies are needed to discover the cross-connections between oxidative stress and disease prevention in signaling pathways networks.