Background: Low-frequency electrical stimulation (LFES) is an adjuvant method for heart failure (HF) patients with restrictions to start an exercise. However, the impact on molecular changes in circulating is unknown. We investigated the effects of 10 weeks of home-based LFES on plasma cytokines profile, redox biomarkers, metalloproteinases (MMPs) activity, and exercise performance in HF patients. Methods: Twenty-four HF patients (52.45 ± 9.15 years) with reduced ejection fraction (HFrEF) (EF < 40%), were randomly assigned to a home-based LFES or sham protocol. Plasma cytokines profile was assessed through interleukins, interferon-gamma, and tumor necrosis factor levels. Oxidative stress was evaluated through ferric reducing antioxidant power, thiobarbituric acid-reactive substances, and inducible nitric oxide synthase. The MMPs activity were analyzed by zymography. Cardiorespiratory capacity and muscle strength were evaluated by cardiopulmonary test and isokinetic. Results: LFES was able to increase the active-MMP2 activity post compared to pre-training (0.057 to 0.163, p = 0.0001), while it decreased the active-MMP9 (0.135 to 0.093, p = 0.02). However, it did not elicit changes in cytokines, redox biomarkers, or exercise performance (p > 0.05). Conclusion: LFES protocol is a promising intervention to modulate MMPs activity in HFrEF patients, although with limited functional effects. These preliminary responses may help the muscle to adapt to future mechanical demands dynamically.