Stroke is characterized by a sudden onset of neurological deficit attributed to a focal brain injury. The main treatments for patients with an acute ischemic stroke are intravenous thrombolysis and mechanical thrombectomy. Recanalization therapies have significantly improved patient outcomes; however, their effectiveness depends on a range of pathophysiological factors. This prospective observational study included 60 patients with acute ischemic stroke. The control group consisted of 20 healthy blood donors. Patients were divided into three groups based on whether they received intravenous thrombolysis, mechanical thrombectomy, or combination therapy. We investigated differences between recanalization therapies in patients with ischemic stroke with respect to peripheral blood concentrations of the proinflammatory cytokine interleukin (IL)-18 and endothelial glycocalyx degradation products: syndecan-1, heparan sulphate, and hyaluronic acid, measured by enzyme-linked immunosorbent assay. The blood samples were collected before, 24, and 48 h after recanalization therapy. The concentration of IL-18, syndecan-1, and heparan sulphate increased statistically significantly in patients treated with mechanical thrombectomy. The concentration of hyaluronic acid increased statistically significantly in patients treated with intravenous thrombolysis. The findings primarily reflect between-group differences. Our findings indicate that IL-18 has a significant role in the early inflammatory response. IL-18 and EG degradation products represent potential biomarkers for identifying high-risk patients. Their measurement could help improve the treatment, recovery, and outcomes in patients with acute ischemic stroke. The aforementioned observations underscore their potential value as biomarkers for future research.