Curcumin and eugenol have been appreciated as broad-spectrum antimicrobial agents since the early 20th century, and their parent plants of turmeric and clove have been used in Ayurvedic and traditional Chinese medicines for thousands of years. Although extensive research has identified several antimicrobial mechanisms of action, it is the only eugenol that has become established for dental uses. Curcumin and eugenol have been hard to purify and stabilize and, in their native states, show poor bioavailability. New antimicrobial agents are now needed due to the growth in resistant strains, and this means natural agents are back in vogue. Nanoparticle and antimicrobial-coated surfaces are popular strategies to maximize the consistent delivery of mainstream pharmaceuticals. Computational chemistry and docking analyses are the primary methods used to identify and design novel variants of natural molecules to improve bioavailability and stability. Both curcumin and eugenol have benefitted from the expansion of these fields, and reports of stabilized forms with superior activity are now rapidly appearing in the literature. This chapter will review the antimicrobial spectrum of curcumin and eugenol, explaining their antimicrobial modes of action. Finally, potential and currently available delivery systems will be explored using the semi-synthetic analogs and bioengineered structures that have been created.