BACKGROUND: Diabetes mellitus (DM) presents a significant global health challenge with considerable cardiovascular implications. Coenzyme Q10 (CoQ10) has gained recognition for its potential as a natural antioxidant supplement in the management of diabetes and its associated cardiovascular complications. AIM: This comprehensive review systematically examines the scientific rationale underlying the therapeutic properties of CoQ10 in mitigating the impact of diabetes and its cardiovascular consequences. The analysis encompasses preclinical trials ( and ) and clinical studies evaluating the efficacy and mechanisms of action of CoQ10. . Findings reveal that CoQ10, through its potent antioxidant and anti-inflammatory attributes, demonstrates significant potential in reducing oxidative stress, ameliorating lipid profiles, and regulating blood pressure, which are crucial aspects in managing diabetes-induced cardiovascular complications. CoQ10, chemically represented as CHO, was administered in capsule form for human studies at doses of 50, 100, 150, 200, and 300 mg per day and at concentrations of 10 and 20 M in sterile powder for experimental investigations and 10 mg/kg in powder for mouse studies, according to the published research. Clinical trials corroborate these preclinical findings, demonstrating improved glycemic control, lipid profiles, and blood pressure in patients supplemented with CoQ10. CONCLUSION: In conclusion, CoQ10 emerges as a promising natural therapeutic intervention for the comprehensive management of diabetes and its associated cardiovascular complications. Its multifaceted impacts on the Nrf2/Keap1/ARE pathway, oxidative stress, and metabolic regulation highlight its potential as an adjunct in the treatment of diabetes and related cardiovascular disorders. However, further extensive clinical investigations are necessary to fully establish its therapeutic potential and assess potential synergistic effects with other compounds.