Metrnl is a secreted protein able to activate different intracellular signaling pathways in adipocytes, macrophages, myocytes and cardiomyocytes with physiological effects of the browning of white adipose tissue (BWT), insulin sensitivity, inflammation inhibition, skeletal muscle regeneration and heart protection. Shown to be regulated by obesity, diabetes, caloric restriction, weight loss and heart diseases, Metrnl is definitely involved in metabolic turbulences, and may play roles in metabolic syndrome (MetS). However, due to the conflicting data yielded, Metrnl is still far from clinical application as a diagnostic and/or a therapeutic agent or even a therapeutic target in MetS-related diseases such as type 2 diabetes (T2D) and obesity. Nevertheless, blood Metrnl levels as well as Metrnl as a cardiokine have been reported to play cardioprotective roles against heart diseases. Considering the established metabolic and anti-inflammatory hallmarks, exercise-induced Metrnl (as a myokine) is regarded as an exercise mediator in improving obesity-induced complications such as insulin resistance, T2D and inflammation. Besides, due to its healing role in muscle damage, Metrnl is also a potential therapeutic candidate to enhance regeneration with ageing or other inflammatory myopathies like Duchenne muscular dystrophy (DMD). Therefore, there are still many exercise-related questions unanswered on Metrnl, such as Metrnl-mediated fat browning in humans, exercise effects on heart Metrnl production and secretion and the effects of other exercise-induced skeletal muscle stressors like hypoxia and oxidative in Metrnl production other than exercise-induced muscle damage.