Nowadays, the global population affront diverse health issues, most of them associated with chronic diseases and infectious illnesses. There is a variety of pharmaceutical drugs that are used to treat these conditions. However, many of these treatments are expensive and have shown to produce side effects in the organism. Therefore, it has become of interest the study of the biological properties of compounds from natural sources that could be employed as alternative treatments for human diseases, without producing adverse effects and being more accessible for the general population. The secondary metabolites, also known as phytochemicals, are compounds produced by plants which have demonstrated biological activities that can contribute to the prevention and treatment of many health issues. Among the diversity of plants distributed around the world, the species of the genus Parthenium have been known to be important sources of numerous groups of phytochemicals such as flavonoids, terpenes, and sesquiterpene lactones, which have exhibited several biological properties that include antioxidant, antitumor, anti-inflammatory, and antimicrobial activities. Hence, the aim of this chapter is to provide a compilation of information previously reported about the phytochemical composition and biological properties of some plants that constitute the genus Parthenium.