Sigesbeckiae Herba is a traditional Chinese herbal medicine and has been used for inflammatory diseases with a long history. The current official plant origins of Sigesbeckiae Herba include Sigesbeckia orientalis L. (SO), S. pubescens Markino (SP) and S. glabrescens Markino (SG). In this work, a systemic review about the scientific work for medicinal Sigesbeckiae Herba regarding their botanical descriptions, reported bioactive components, pharmacological activities and toxicities was performed. The results indicate that a total of 251 compounds including flavonoids, diterpenoids, sesquiterpenoids, triterpenoids, and sterols have been isolated from Sigesbeckia plants and reported to be characteristically distributed in SO, SP and SG. The extracts and pure compounds derived from Sigesbeckiae Herba are reported to present various pharmacological activities including anti-inflammation, immunomodulation, anti-cancer, and others. Although no significant side-effects and toxicities for Sigesbeckiae Herba have been reported in clinics, the potential pulmonary toxicity for the water extracts of SH are reported in experimental animals. In conclusion, Sigesbeckiae Herba is a valuable Chinese herbal medicine and has been investigated to present multiple pharmacological activities. The main pharmacological investigations support its traditional use for treating chronic inflammatory diseases. The available literature shows that much of the activity of Sigesbeckiae Herba can be attributed to diterpenoids, sesquiterpenoids and flavonoids. However, further investigations on the molecular mechanisms to pharmacological activities and the potential toxicities is recommended. Moreover, further investigations on the comparative comprehension among the three medicinal Sigesbeckia plants (SO, SP and SG) both in chemistry and pharmacology are also recommended for their precise applications in clinics.