Mechanical thrombectomy (MT), when combined with intravenous thrombolysis (IVT), has emerged as an effective therapeutic strategy for acute ischemic stroke (AIS). Edaravone Dexborneol, a novel fixed-dose combination of edaravone (30 mg) and dexborneol (7.5 mg) with dual free radical scavenger, has also demonstrated neuroprotective benefits in AIS management. This study aims to investigate the potential effects of Edaravone Dexborneol in patients with AIS who have undergone MT and IVT. This single-center retrospective cohort study enrolled 207 patients with AIS who received both IVT and MT between January 2019 and June 2024. Based on whether they received Edaravone Dexborneol treatment, patients were categorized into the Edaravone Dexborneol group and the control group. Baseline characteristics, inflammatory biomarkers, functional outcomes, mortality, and safety endpoints were compared. Compared to the control group, the Edaravone Dexborneol group showed significantly lower levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and higher levels of anti-inflammatory cytokines (IL-10, IL-35, TGF-β) at Days 3, 7, and 14 (all p < 0.01). Functionally, a greater proportion of patients in the Edaravone Dexborneol group achieved favorable outcomes (mRS 0-2) both at discharge (51.82% vs. 35.05%, p = 0.017) and at 90 days (67.27% vs. 46.39%, p = 0.003). All-cause mortality was numerically lower both in-hospital and at 90 days, without an increase in major safety events, including symptomatic intracranial hemorrhage. Patients treated with Edaravone Dexborneol were associated with better functional outcomes three months after stroke onset compared to those who did not receive the treatment. These findings may be related to the drug's anti-inflammatory properties; however, randomized controlled trials are needed to confirm efficacy in patients undergoing MT combined with IVT.