Pasteurella multocida is a widespread zoonotic pathogen associated with severe hepatic inflammatory responses. Although traditional medicinal plants such as Tribulus terrestris L. (TL) have demonstrated anti-inflammatory properties, their protective effects against Pasteurella multocida-induced liver injury remain insufficiently studied. This study established a Pasteurella multocida-induced liver injury model to evaluate the protective efficacy of TL extract. Thirty-two male Kunming mice were randomly divided into four groups: control, model, penicillin-streptomycin, and TL extract. Therapeutic interventions were conducted by daily intraperitoneal injection of P. multocida (50 CFU/mL) followed by treatment with antibiotics or TL extract (1000 mg/kg/day) for 7 consecutive days. The therapeutic potential of T. terrestris extract was evaluated using histopathological analyses (hematoxylin and eosin (H&E) staining and Masan staining), RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence to assess inflammatory cytokine expression and NF-κB pathway activation. The extract significantly attenuated hepatic fibrosis and inflammatory cell infiltration in infected mice. Following Pasteurella multocida infection, NF-κB pathway activation may indicate by upregulated NF-κB1 and downregulated IκBα expression in mouse liver, alongside increased pro-inflammatory cytokines TNF-α and IL-1β. Treatment with antibiotics or TL reversed these changes. TL likely suppressed NF-κB activation by downregulating receptor TNFRsf1a. Immunohistochemistry and immunofluorescence further demonstrated decreased phosphorylation of IκBα and reduced IL-1β and TNF-α after treatment, indicating effective inhibition of NF-κB signaling and inflammation. These effects were comparable to those observed with antibiotic treatment. Our research reveals that TL extract alleviates Pasteurella multocida-induced hepatic inflammation by inhibiting NF-κB activation, highlighting its potential as a plant-derived therapeutic agent for bacterial liver injury.