Heart failure (HF) is associated with a deficiency in blood levels of coenzyme Q10 (CoQ10), and its supplementation has been proposed. The aim of this systematic review was to synthesise the available evidence on the effects of CoQ10 on cardiac function and quality of life in HF. A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted from inception until March 2023. Meta-analyses measuring the effect of CoQ10 on cardiac function [i.e., ejection fraction (EF), cardiac output (CO), cardiac index (CI), stroke volume (SV)], quality of life [i.e., mortality, exercise capacity, and New York Heart Association (NYHA) classification], and CoQ10 levels in HF were included. Ten meta-analyses met the inclusion criteria. CoQ10 had an effect on EF in 6 of the 9 studies, with an increase of 1.77% (0.10, 3.44) to 3.81% (1.22, 6.40), while it had an effect on CO, CI and SV in one of the two studies. Moreover, CoQ10 did not improve exercise capacity and only one study showed an effect on NYHA classification, while there was a risk ratio (RR) of 0.69 (0.50, 0.95) to 0.58 (0.35, 0.95) in favour of CoQ10 for mortality and a RR of 0.62 (0.49, 0.78) for hospitalisations. Finally, CoQ10 levels were found to increase by 1.40 μg mL-1 in all studies. CoQ10 showed a possible beneficial effect on heart function, which was associated with a reduction in mortality and hospitalisations. However, more research is needed into the conditions that may optimise CoQ10 therapy.