Coffee, cinnamon, and ginger are natural products rich in bioactive compounds that have led to renewed interest to validate their health benefits through in vitro and in vivo studies. This chapter describes several mechanisms of action to understand their antioxidant, antidiabetic, anti‐inflammatory, cardioprotective, and hepatoprotective effects observed in preclinical and clinical studies. Coffee, ginger, and cinnamon were selected for this chapter because coffee is one of the most consumed beverages in the world, and ginger rhizome and cinnamon bark are among the most commonly used spices for their flavor and medicinal properties. All contain bioactive substances responsible for or attributable to their beneficial health effects, among which are caffeine and gallic acid from coffee, gingerols, shogaols, and paradols from ginger, cinnamaldehyde, cinnamate, and cinnamic acid of cinnamon among others phytochemicals. The molecular mechanisms involved in the antioxidant effects are associated with the activation of Keap1‐Nrf2 pathway that enhances the expression and activation of cytoprotective proteins to prevent oxidative stress. The molecular mechanisms involved in the antidiabetic potential are related to the modulation of glucose metabolism enzymes, increase of glucose tolerance, and insulin sensitivity through the action signaling pathways such as AMPK, PI3K/Akt, NF‐κB, and the family of proliferator‐activated receptor (PPAR) proteins. Cardiovascular protection capacity has been attributed to modulating the expression of Sirtuin 1 (SIRT1), carbohydrate response element binding protein (ChREBP), cholesterol and fatty acid synthesis enzymes, sterol regulatory Element‐Binding Protein 1 (SREBP‐1), the Liver X Receptor alpha, PPARα, and PPARγ. The hepatoprotective benefits of coffee have been associated with TGFβ and JNK modulation, fibrogenic genes suppression, and of NFκβ and MAPK pathways modulation, whereas ginger and cinnamon reduce the expression of different proteins involved in lipid metabolism; in addition, ginger increases liver antioxidant capacity and cinnamon reduces proinflammatory proteins. Finally, the molecular signaling of anti‐inflammatory effects occurs through activation of the TLR4/MyD88/NF‐κβ, JNK/AP‐1, PI3K/Akt, and ERK/MAPK signaling pathways and the subsequent downregulation of proinflammatory cytokines. The available scientific evidence indicates that they are potential natural sources for the development of functional foods and new drugs with greater efficacy and safety.