Mu-opioid receptor is an important member of G-protein-coupled receptor family, which is widely distributed in the nervous system. It is the core target of regulating pain signal transmission, and also the key molecule involved in reward loop, emotional regulation and neural plasticity. Traditional opioid drugs play a powerful analgesic role by activating mu-opioid receptor, but long-term use is easy to cause substance abuse, resulting in tolerance, dependence and addiction, and its mechanism is closely related to the imbalance of signal pathway mediated by mu-opioid receptor, neuroinflammatory response and synaptic function remodeling. In recent years, with the in-depth study on the conformational dynamics of mu-opioid receptor, ligand functional selectivity and downstream signal network, biased agonists or allosteric modulators of mu-opioid receptor may reduce the risk of addiction while retaining analgesic activity. In this paper, the distribution and function of mu-opioid receptor in nervous system are systematically reviewed, the molecular mechanism of addiction development is expounded, and the current drug research and development strategies and research progress based on mu-opioid receptor are summarized, so as to provide new ideas for clinical optimization of opioid drug use scheme and development of low addictive analgesic drugs.