Cholangitis and cholestasis are significant hepatobiliary disorders characterized by impaired bile flow and inflammation of the bile ducts, leading to severe complications such as liver damage, infections, and increased morbidity. Primary biliary cholangitis (PBC), a progressive autoimmune disease characterized by bile duct damage and autoantigen generation, disproportionately affects females, with a median female-to-male ratio of 10:1. This study evaluated the therapeutic potential of olive leaf extracts, prepared using two different extraction methods, against α-naphthyl-isothiocyanate (ANIT)-induced cholangitis and cholestasis in rats. Forty rats were divided into four groups: G1 (control), administered saline solution (0.9% NaCl); G2 (PBC), induced with ANIT (1 g/kg powdered rat chow); G3 (PBC + OL-Etha), treated with olive leaf extract obtained via simple extraction (400 mg/kg/day b.w.); and G4 (PBC + OL-Sox), treated with olive leaf extract obtained via Soxhlet extraction (400 mg/kg/day b.w.). ANIT-treated rats exhibited significant liver damage, as evidenced by elevated biomarkers of liver dysfunction, cholangitis, and cholestasis, along with increased levels of TNF-α, IL-1β, and antimitochondrial antibodies (AMA-M2). Histological analysis confirmed these findings. Treatment with olive leaf extracts significantly reduced liver function test markers, indices of cholangitis, inflammatory cytokines, AMA-M2 levels, and improved anthropometric measurements, gene expression of TGF-β, and histological alterations. The study concluded that olive leaves contain bioactive compounds with antioxidant and anti-inflammatory properties that mitigate ANIT-induced cholangitis and cholestasis by regulating oxidative stress and inflammatory pathways. Primarily, the Soxhlet extraction method was more effective in isolating active components compared to the methanolic maceration method.