Lipopolysaccharide (LPS)-induced inflammatory liver injury can cause significant tissue damage and apoptosis. Homeopathic formulations such as Tarantula cubensis venom show potential in regulating inflammation. This study's objective was to assess theranecron's (THE) impact on inflammation and oxidative stress in a model of liver injury caused by lipopolysaccharide (LPS). Wistar albino female rats were used in this investigation, and they were split up into four groups of eight each: Control, LPS, LPS+THE, and THE. Single-dose treatments were administered to the respective groups on the same day. Liver tissues were collected 6 h after LPS treatment for histopathological, immunohistochemical, biochemical, and genetic evaluations. Total antioxidant status (TAS) was lower, total oxidant status (TOS) and oxidative stress index (OSI) were higher, and the LPS group had higher levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and macrophage antigen-1 (CD11B). Significant liver damage was also seen in this group, as evidenced by elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased albumin. Nuclear factor erythroid 2-related factor 2 (Nrf2), Sirtuin 1 (SIRT1), heme oxygenase 1 (HO-1), kelch-like ECH-associated protein 1 (Keap1), and glutathione peroxidase 4 (GPx4) were all found to be downregulated by gene expression analysis. However, THE therapy was shown to reverse all of these findings in the LPS+THE group. The THE group similarly maintained baseline levels of these markers and showed no adverse effects. In conclusion, Theranekron showed hepatoprotective effects in LPS-induced liver injury by reducing oxidative stress and inflammation and regulating antioxidant gene expression, possibly through IL-6 and TNF-α.