Retinoic acid-related orphan receptor RORγt plays a pivotal role in the differentiation of Th17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat Th17-related autoimmune diseases. In this report, we present the identification of a series of diphenylpropanamides as novel and selective RORγt antagonists. ML209 inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed Th17 cell differentiation at submicromolar concentrations.