Curcuma longa L. (C. longa), more commonly known as turmeric, is a spice used in treating various diseases traditionally. Some of the traditional applications including anti-inflammatory, anticancer, and liver protective activities of turmeric have been validated in a number of cell- and animal-based studies where many of the bioactivities were found to be associated with curcumin, the most abundant curcuminoid in the rhizome of C. longa. Curcuminoids represent the most abundant, and thus most widely studied group of more than 200 compounds that have been identified in C. longa. Besides curcuminoids, sesquiterpenes is another important group of active compounds in C. longa that have also been shown to enhance the bioactivities of curcumin. In this chapter, we hope to provide an overview of the reported bioactivities of the major sesquiterpenes in C. longa. Greater emphasis is given to bisabolane-type sesquiterpenes and β-elemene, which represent the major group of non-curcuminoids and the most extensively studied non-curcuminoid of C. longa, respectively.