<p>We aimed to investigate the effects of Xuebijing (XBJ) combined with levosimendan on the immune function and coagulation function in patients with sepsis complicated by myocardial injury. This double-blind, randomized controlled trial involved 88 sepsis patients with myocardial injury, split into control (<i>n</i> = 44, levosimendan plus conventional therapy) and combination (<i>n</i> = 44, control group’s treatment plus XBJ injection) groups. Primary outcomes: coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT), fibrinogen (Fib), and D-dimer (D-D)], immune function indicators (peripheral blood T lymphocyte subsets: CD4+, CD8+, and the CD4+/CD8+ ratio). Secondary outcomes: inflammatory markers [procalcitonin (PCT), C-reactive protein (CRP), and tumor necrosis factor (TNF-α)], vascular endothelial function markers [endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and soluble thrombomodulin (sTM)], myocardial function biomarkers [cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and B-type brain natriuretic peptide (BNP)], and hemodynamic parameter [heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP)]. Post-treatment, serum levels of PCT, CRP, TNF-α, ET-1, vWF, sTM, PT, APTT, D-D, CD8+, cTnI, CK-MB, BNP, and HR were lower in both groups, with further reductions in the combination group. Levels of NO, VEGF, PLT, Fib, CD4+, CD4+/CD8+ ratio, MAP and CVP were higher in the combination group than in the control group (all <i>P</i> &lt; 0.05). The combination of XBJ and levosimendan improves coagulation function, regulates immune function, enhances vascular endothelial function and hemodynamics, reduces inflammation, and alleviates myocardial injury.</p>