Growth differentiation factor 15 (GDF15) is strongly associated with metabolic dysfunction-associated steatohepatitis (MASH), yet whether it drives disease or protects against liver injury remains unresolved. Using thermoneutral mouse models that closely mimic human MASH, we show that loss of GDF15 or its receptor GFRAL selectively worsens hepatic inflammation and fibrosis independently of steatosis or insulin resistance. Conversely, recombinant GDF15 suppressed liver inflammation and fibrosis more effectively than matched caloric restriction despite equivalent reductions in food intake, body weight, and steatosis. Spatial transcriptomics and bulk RNA-seq revealed that GDF15 remodels the hepatic immune-fibrotic niche by suppressing pro-inflammatory macrophages, plasma B cells, and activated stellate cells while promoting pro-resolving immune programs. These effects required GFRAL but occurred independently of β-adrenergic signaling. In a steatosis-free CCl₄ model, GDF15 retained potent anti-inflammatory effects and activated hypothalamic-pituitary-adrenal (HPA) axis and hepatic glucocorticoid receptor (GR) signaling, which were blunted by GR antagonism. Together, these findings identify GDF15 as an endogenous neuroimmune regulator that restrains liver inflammation and fibrosis independently of weight loss or steatosis through a GFRAL–HPA–GR signaling axis.