Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that α-lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects of α-lipoic acid. It highlights the fact that α-lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.