Abstract: Opioid analgesics, which primarily exert their effects through μ-opioid receptors, have long been valuable choices in pain management. However, opioid analgesics often cause various adverse reactions that are common to traditional opioids, especially respiratory depression. With the continuous advancement of research, it has been discovered that activation of the μ-opioid receptor triggers two distinct signaling pathways: the G-protein pathway, which mainly mediates analgesic effects, and the β-arrestin pathway, which is associated with side effects such as respiratory depression and constipation. This finding provides a theoretical basis for separating the analgesic effects from the adverse reactions of opioid drugs. Therefore, recent years have seen significant attention to the development and application of biased opioid receptor agonists in clinical settings. This review summarizes the research progress on biased μ-opioid receptor agonists, and provide evidence for the clinical use and development of opioid drugs.