Janus kinase/signal transducer and activator of transcriptions (JAK/STAT) signaling pathway is one of the major signaling pathways involved in a variety of human physiological and pathological process. The proteins of JAK/STAT pathway or interferon response element (such as JAK, STAT, Src, SOCS, 2'5'-OAS, and ISRE) might be as drug targets for the study of physiological processes and treatment of related diseases, including cell proliferation, differentiation, apoptosis and immune processes, inflammation, cancer, arthritis, asthma, diabetes, and other diseases. This review attempts to summarize the current status of natural products and their derivatives (2002-2013) regulating the proteins or transcription elements of JAK/STAT signaling pathway to supply a new direction or drug targets for the discovery of new drugs.