Background <p>High-intensity interval training (HIIT) is an effective strategy to improve age-related cardiometabolic risk. Coenzyme Q10 (CoQ10), a mitochondrial cofactor and antioxidant, may potentiate exercise-induced metabolic adaptations<b>.</b></p> Aim <p>This study examined whether combining CoQ10 with HIIT provides additional metabolic benefits in older adults.</p> Methods <p>Thirty-eight healthy older adults (65–75 years) were randomly assigned to HIIT + CoQ10 (<i>n</i> = 19) or HIIT + placebo (<i>n</i> = 19) for 8 weeks (three sessions per week). Participants received 100 mg/day of CoQ10 or placebo. Fasting glucose (FBG), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (vLDL), and liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured before and after the intervention.</p> Results <p>Both groups demonstrated significant improvements in glycemic indices, lipid profile, and liver enzymes over time (<i>p</i> &lt; 0.05). Significant time × group interactions were observed for insulin, HOMA-IR, TC, TG, LDL-C, and vLDL, indicating greater improvements with HIIT + CoQ10. No additive effect of CoQ10 was observed for ALT or AST.</p> Discussion <p>Eight weeks of HIIT improved cardiometabolic health in older adults. Both HIIT + CoQ10 and HIIT + placebo groups showed improvements in glycemic indices and lipid profile, but CoQ10 further enhanced insulin sensitivity and lipid metabolism, suggesting that it may potentiate exercise-induced metabolic adaptations.</p> Conclusion <p>HIIT improves cardiometabolic health in older adults, with CoQ10 further enhancing insulin sensitivity and lipid metabolism.</p> Trial registration <p>IRCT20240310061243N1. Registered 10 March 2024 (retrospectively registered).</p>