Sepsis presents a significant global health threat, characterized by systemic inflammatory responses and cardiac sepsis infections, often triggered by gram-negative bacteria, resulting in severe inflammatory reactions, multiorgan failure, and high mortality rates. Diosmin, known for its phlebotonic properties enhancing vein health, possesses notable anti-inflammatory, antioxidant, and anti-mutagenic attributes. This study examines Diosmin's cardioprotective potential in Lipopolysaccharide (LPS)-induced cardiac dysfunction using both in- silico docking and experimental approaches. In-silico docking studies revealed Diosmin's interactions with target proteins, demonstrating higher docking scores and unique interactions compared to Imatinib, suggesting its potential to mitigate Imatinib effects. Experimental protocols employed albino Wistar rats (weighing 180-200g, with n=5-6 per group), wherein cardiac dysfunction was induced by administering LPS (10mg/kg i.p) commencing on the 14th day of the study. Diosmin (50 and 100 mg/kg, p.o.) and Imatinib mesylate (30mg/kg, p.o.) were administered as pretreatment for two weeks. Furthermore, Diosmin exhibited comparable interactions with Montelukast, highlighting its versatile therapeutic potential. Throughout the study, Diosmin significantly attenuated the aberrant metabolic alterations in LPS-treated rats. Treatment showed notable benefits in alleviating LPS-induced cardiac dysfunction, as evidenced by hemodynamic studies, biochemical assays, tissue estimations, and histopathological examinations, revealing dose-dependent improvements in cardiac biomarkers and functional parameters. However, experimental validation remains crucial despite promising in-silico predictions. In conclusion, Diosmin shows promise in ameliorating LPS-induced cardiac dysfunction due to its anti-inflammatory and antioxidant properties. Synergistic effects with Imatinib and in-silico findings underscore Diosmin's potential, urging rigorous experimental validation for addressing sepsis-related cardiac complications.