Opioid-induced constipation is the most common and difficult-to-treat gastrointestinal adverse effect of opioids. Peripherally acting mu-opioid receptor antagonists (PAMORA) class, to which naldemedine belongs, provide causal treatment. Almost half of the patients have a bowel movement within 4 hours after the first dose and two-thirds within 24 hours. Naldemedine does not reverse opioid analgesia, nor does it cause withdrawal symptoms, even over months of use. In 40% of cancer patients, it restores the acceptable frequency of at least 3 bowel movements per week. At an oral dose of 0.2 mg once a day, it is a convenient treatment and secondary prophylaxis of opioid constipation in patients taking any opioid analgesic. Based on good-quality clinical evidence, orally administered naldemedine is recommended as an effective, well-tolerated, and convenient treatment of opioid-induced constipation without the need to modify pain management. Naldemedine has been reported to be effective in opioid side effects other than constipation, such as nausea and vomiting. This narrative review presents state of the art and practical aspects of the treatment of opioid-induced intestinal disorders with naldemedine.