Considering the great importance of the GDF15/GRAL/RET signalling pathway, this review focuses on GDF15‐derived analogues able to act either as GFRAL agonists or antagonists, investigating their possible pharmacological applications in the treatment of GDF15‐related conditions, such as obesity and diabetes (agonist), or cancer‐induced nausea and cachexia (antagonist). This evidence concerns the gene GFRAL and cancer.