Abstract: Against the backdrop of a continuously evolving global opioid crisis, the illicit drug market is undergoing a rapid shift from fentanyl analogs to novel non-fentanyl synthetic opioids (NFSOs). Following the widespread international scheduling of nitazenes, orphines have rapidly emerged as the next generation of substitutes. Orphines belong to the class of benzimidazol-2-one novel synthetic opioids, characterized by high potency, strong toxicity, and difficulty in detection, posing a significant global public health threat. Based on existing literature, this article systematically reviews the structural classification, pharmacological and toxicological characteristics of orphines, summarizes research progress on derivatives such as brorphine, chlorphine, and 5,6-dichloro desmethylchlorphine, consolidates relevant case reports, and synthesizes findings from studies on detection and risk assessment. This review aims to provide a scientific basis for the monitoring, prevention and control, clinical management, and forensic identification of these substances.