Abstract: Objective To investigate the effect of metadoxine combined with naloxone on therapeutic efficacy in patients with acute alcohol intoxication. Methods A total of 88 patients with acute alcohol intoxication admitted to the Hepatology Department of Boao International Hospital of Shanghai University of Traditional Chinese Medicine from April 2023 to April 2024 were selected. Patients were numbered sequentially based on their admission time and randomly divided into a naloxone group (44 cases) and a metadoxine combination group (44 cases) using a random number table. Symptom indicators, blood gas parameters partial pressure of carbon dioxide in arterial blood (PaCO₂), arterial partial pressure of oxygen(PaO₂), pH values, liver and kidney function indicators alanine aminotransferase (ALT), aspartate transferase (AST), creatine kinase (CK), serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress levels superoxide dismutase (SOD), malondialdehyde (MDA) were compared between the two groups. Results Symptom relief time, symptom disappearance time, consciousness recovery time, and hospitalization duration in the metadoxine combination group were all shorter than those in the naloxone group (two-sided P values ＜ 0.05); After 1 and 5 days of treatment, pH values and PaO₂ levels in the metadoxine combination group were higher than those in the naloxone group, while the PaCO₂ levels were lower than those in the naloxone group (two-sided P values ＜ 0.05). After 1 and 5 days of treatment, the levels of ALT, AST, CK, Scr, and BUN in the metadoxine combination group were lower than those in the naloxone group (two-sided P values ＜ 0.05). After 1 and 5 days of treatment, serum SOD levels in the metadoxine combination group were higher than those of the naloxone group, while the MDA levels were lower than those in the naloxone group (two-sided P values＜ 0.05). Conclusion The combination of metadoxine and naloxone in the treatment of acute alcohol intoxication patients can improve blood gas parameters, alleviate liver and kidney function damage, reduce oxidative stress levels, and promote symptom resolution.