Toll-like receptors are transmembrane proteins which sense and transmit infectious and inflammatory responses to the cells expressing them. Therapeutic strategies for the blockade of excessive Toll-like receptor signaling are being actively pursued for several diseases. Recently, Sparstolonin B, isolated from Chinese herb, which suppresses selectively Toll-like receptors has been studied in various inflammatory models. The objective of this review is to summarize the current literature regarding the use of Sparstolonin B in various in vitro and in vivo studies and to provide an overview regarding the potential use of this agent in different inflammatory diseases. Additionally, the current knowledge regarding the role of Toll-like receptors in inflammatory disease and the usage of various Toll-like receptor antagonists will be summarized. Based on our review, we believe Sparstolonin B could serve as a potential therapeutic agent for treatment of Toll-like receptor-mediated inflammatory disorders.