This study evaluates the clinical efficacy of activated charcoal combined with mannitol (ACM) for the treatment of Haff disease. This is a retrospective cohort study conducted at the Emergency Department of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. Consecutive patients who were hospitalized during a two-year time frame (from June 2016 to August 2017) and diagnosed with Haff disease were reviewed. Clinical symptoms, laboratory findings, pain/anxiety scores, and treatment-related adverse events were collected. Sixty-eight Haff disease patients after boiled crayfish consumption were enrolled in this study. Besides standard treatments for Haff disease, 22 patients had an oral administration of activated charcoal and mannitol within 12 hours of hospital admission (ACM group), while the other 46 patients did not receive such treatment (non-ACM group). Baseline characteristics including clinical symptoms, serum enzyme levels, and pain/anxiety scores were comparable between the two groups. Activated charcoal and mannitol treatment led to lower CK-MB and AST levels from 12 hours to 60 hours, lower ALT and LDH levels from 12 hours to 72 hours, and lower CK levels from 24 hours to 72 hours after hospitalization. Patients in the ACM group had significantly shortened duration of hospital stays (7.5 [6.0–8.0] days vs 8.0 [6.8–10.0] days, p=0.032) and lower anxiety scores 24 hours after hospital admission (40.7 ± 4.9 vs 44.1 ± 6.3, p=0.032) than in the non-ACM group. No patient experienced treatment-related adverse events. The overall prognosis of both groups is good. Among patients with Haff disease caused by boiled crayfish, activated charcoal combined with mannitol treatment resulted in shorter hospital stays, lower serum CK, CK-MB, AST, ALT, and LDH levels, and lower anxiety scores.