Myonectin, a novel muscle-derived peptide or myokine, has been implicated in glucose and lipid homeostasis through its autocrine, paracrine, and endocrine functions. This review aimed to explore the impact of structured exercise interventions on myonectin levels and insulin resistance indicators in healthy individuals and those living with overweight or obesity. We performed a search of PubMed, Science Direct, CINAHL, TRIP Database, Cochrane Library, and Google Scholar for studies published until July 2022. The key terms used were “prediabetes”, “overweight”, “obesity”, “myonectin”, “Complement 1q / tumor necrosis factor-related protein 5 (CTRP5 or C1qTNF5)”, “erythroferrone”, and “exercise”. Eight studies investigated the effects of exercise on myonectin levels and insulin resistance, measured through the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), in individuals who were overweight or obese, while six studies focused on those without these conditions. After data extraction, narrative qualitative synthesis and risk of bias analysis were performed. Findings indicate that structured aerobic or combined aerobic and resistance training at moderate intensity over 8–12 weeks led to significant increases in myonectin levels and reductions in insulin resistance, particularly among women who were overweight or obese. However, data was limited by heterogeneous age and gender groups’ metabolic profiles and variability in exercise protocols. Myonectin response to exercise in healthy adults remains unclear due to baseline metabolic variability, though some improvements in the glucose-insulin axis were noted. This review suggests that myonectin may serve as a valuable biomarker to assess the impact of exercise on insulin sensitivity in individuals at risk of diabetes with overweight or obesity.