Abstract: Glucagon-like peptide-1 (GLP-1) receptor agonists account for an increasing proportion of the market of anti-diabetic and weight-reducing medicines with its unique advantages. However, due to the heterogeneity and concomitant pathological features of obesity and type 2 diabetes as well as the complexity of energy balance regulation, its moderate weight-reducing effect cannot achieve the desired results. Single-molecule multi-receptor agonists based on GLP-1 are expected to improve metabolic disorders by integrating the beneficial effects of several gut hormones. On the basis of the molecular structures and clinical data of GLP-1 analogues on the market, this review focuses on the research progress of various GLP-1-based single-molecule multi-target agonists to provide new approaches to the maintenance of blood sugar homeostasis and anti-obesity therapies.