<p>Treatment resistance in bipolar disorder (BD) is common, and innovative treatments are needed. The opioid system is under investigation as a new target treatment of depression and BD, notably the treatment of depressive symptoms. This narrative review aims to synthesize the evidence related to opioid-receptor-modulating drugs in treating BD. The protocol was preregistered at Open Science Framework. A search of the literature databases Embase, PubMed, and PsycINFO was conducted in March 2024 for studies involving the treatment of manic or depressive symptoms of BD with an opioid-receptor-modulating drug. The studies revealed a preliminary antimanic but transient effect of intravenous naloxone and potential antimanic effects of pentazocine. Methadone showed an effect on regulating manic symptoms. The existing evidence on the effects of opioid-receptor-modulating drugs in BD is scarce, and most studies are older and based on small samples. Clinically, opioid-receptor-modulating drugs cannot be recommended or integrated into the treatment of BD. Still, well-designed, randomized controlled trials are needed to draw any firm conclusions.</p>