Statins are effective drugs for lowering hypercholesterolemia and preventing cardiovascular diseases. They can cause various side effects, in particular statin-associated muscle symptoms (SAMS) associated with mitochondrial dysfunction and micronutrient depletion. The aim of this systematic review and meta-analysis was to investigate the efficacy of a supplementation with Coenzyme Q10 (CoQ10) against SAMS in statin-treated patients. A systematic literature search was performed in Medline and Cochrane Library in August 2024. Studies were selected for a meta-analysis according to the following criteria: randomised controlled trials (RCTs), adults taking statins (any type and dose), supplementation of CoQ10, a comparable control group, and muscle pain as outcome criterion. Cochrane Risk of Bias tool was used for bias assessment. Seven RCTs with 389 patients in total were included in this meta-analysis. The selected studies included 35 to 76 patients and had a duration ranging from 30 to 90 days with CoQ10 dosages ranging from 100 to 600 mg per day. Results show a significant reduction of SAMS in four trials and no significant change in three trials. Overall, a significant reduction in SAMS, measured as pain intensity, after CoQ10 supplementation was found: weighted mean difference (WMD) −0.96 (95% Confidence Interval −1.88; −0.03), p < 0.05. Supplementation of CoQ10 can reduce muscle pain in patients with SAMS, which is relevant for their well-being and treatment continuation. More research is needed for evidence-based recommendations.