The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial. PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg–Mazumdar correlation test. Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, − 2.12; 95% CI, − 3.40 to − 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, − 1.91; 95% CI, − 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, − 2.36; 95% CI, − 4.30 to − 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, − 0.20; 95% CI, − 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, − 2.403; 95% CI, − 3.992 to − 0.813; p < 0.001) and high intensity statins (SMD, − 1.727; 95% CI, − 2.746 to − 0.709; p < 0.001) decreased circulating CoQ10. Meta-regression showed that the effect of statin on decreasing circulating CoQ10 was not closely associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Statin treatment decreased circulating CoQ10 but was not associated with the statin solution, intensity, or treatment time. The findings of this study provide a potential mechanism for statin-associated muscle symptoms (SAMS) and suggest that CoQ10 supplementation may be a promising complementary approach for SAMS.