Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide, characterized by hepatic steatosis accompanied by inflammatory responses and progressive fibrotic changes. In recent years, plant-derived extracellular vesicle-like particles (PEVLPs) have attracted increasing attention due to their notable therapeutic advantages, and their potential in MASLD has been explored across various plants. However, the role of extracellular vesicle-like particles (EVLPs) derived from Exocarpium Citri Grandis (ECG) in MASLD remains unclear. In this study, an EVLP-enriched preparation derived from ECG (ECG-EVLPs) was prepared, and its therapeutic potential as well as underlying mechanisms in MASLD were investigated. Our results demonstrated that ECG-EVLPs effectively ameliorated MASLD. ECG-EVLPs were characterized as spherical nanoparticles with a membrane structure, an average diameter of 131.2 nm, and favorable colloidal stability. ECG-EVLPs showed no detectable cytotoxicity under the tested conditions, and their oral administration resulted in liver-enriched fluorescence signals. Functional studies showed that ECG-EVLPs dose-dependently reduced lipid accumulation in hepatocytes and markedly alleviated hepatic steatosis, inflammatory injury, and early fibrotic alterations in MASLD mouse models. Integrated transcriptomic analyses combined with functional validation suggested HOXC6 as a candidate regulatory node associated with the effects mediated by ECG-EVLPs. Both ECG-EVLP administration and HOXC6 knockdown were accompanied by reduced ERK1/2 phosphorylation and downregulation of SREBP1c expression. Notably, pharmacological reactivation of ERK1/2 partially restored SREBP1c expression and reversed the reductions in lipid accumulation and inflammatory cytokine production induced by HOXC6 knockdown. Overall, these findings suggest that ECG-EVLPs may serve as a candidate plant-derived formulation for MASLD, potentially acting through a HOXC6-associated regulatory axis involving ERK1/2-SREBP1c signaling.