Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β (TGF-β) superfamily, is widely expressed in multiple tissues. Under normal physiological conditions, the expression of GDF15 is low in all tissues except for placenta and prostate. However, with aging and exercise or stress stimulation, the GDF15 level is significantly increased. GDF15 binds its reporter, glial cell line derived neurotrophic factor family receptor α-like (GFRAL), to induce the intracellular fatty acids β oxidation and lipolysis, subsequently alleviating the development of fatty liver and inhibiting obesity through decreased food intake. GDF15 is also considered as an inflammatory factor regulating aging and fibrosis related diseases. This article mainly summarizes the regulatory role of GDF15 in aging, metabolism and inflammation-related diseases, so as to provide insights for the treatment strategies targeting GDF15.