T helper 17 (Th17) cells have been implicated in numerous inflammatory autoimmune diseases. Clinical benefits from targeting Th17 cell-related cytokines, such as IL-17 and IL-23, highlight how knowledge of Th17 cell development and effector function can be translated into treatments for inflammatory disease. Here we discuss the pathogenic roles of Th17 cells in autoimmune diseases such as multiple sclerosis, inflammatory bowel disease and psoriasis, with emphasis on the cytokines, transcriptional regulators and metabolites that influence Th17 cell differentiation and pathogenicity. Moreover, we address how intestinal environments and physiological responses affect Th17 cells in autoimmune diseases. We also examine current and emerging therapeutic strategies aimed at regulating Th17 cell-driven inflammation to mitigate autoimmune diseases.