The dried fruits of Ligustrum lucidum Ait. are well-established in East Asian medicine for hepatoprotection. Given this ethnopharmacological precedent and their close taxonomic kinship, we hypothesized that the fruit polysaccharide of its horticultural congener, Ligustrum × vicaryi L. (LVFP), may confer analogous hepatic benefits. We assessed LVFP in a murine model of acute liver injury (ALI) induced by lipopolysaccharide and D-galactosamine (LPS/D-GalN) to test this hypothesis. LVFP pretreatment significantly mitigated hepatic pathological damage, normalized serum aminotransferases (AST, ALT), and reversed lipid peroxidation (reduced MDA, elevated SOD). Simultaneously, LVFP reduced pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and corrected lipid metabolic abnormalities (CHO, TG). To decode these phenotypic rescues, network pharmacology and molecular docking nominated a 10-gene hub signature (featuring KDR (binding energy = −8.65 kcal/mol), AKT1, GSK3B, and IL2). we further found that this signature—particularly KDR and PKM—robustly discriminates ALI from controls (AUC = 1.00; AUPR = 0.848), supporting its disease relevance. Collectively, these findings support our initial hypothesis that LVFP exerts multi-dimensional hepatoprotection.