Aims: Olanzapine/samidorphan (O/S) is a novel drug for use in schizophrenia in adults, and in bipolar I disorder. We aim to mine and evaluate AE signals created by O/S using the FAERS database. Methods: The reporting odds ratio, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker methods were used to first demonstrate the relationship of O/S with AEs from May 2021 to June 2024 using the FAERS database. Results: A total of 1964 AE reports of O/S as the “primary suspect” were collected. A total of 70 preferred term signals and 23 system organ classifications were obtained, mainly concentrated in psychiatric disorders (19.30%). The mean time to onset of O/S-related AEs was 17 days. In addition to the known AEs, more than 20 novel potential AEs were identified, such as oedema peripheral, dysarthria, and euphoric mood. Notably, risk signal for suicidal ideation was detected in this study. In addition, some uncommon but relatively strong AE signals were also observed, such as hallucination, auditory, and aggression. Meanwhile, drug screen false positive exhibited extremely high signal intensity. It is suggested that special attention should be paid to these potential AEs when using O/S clinically. Conclusion: In clinical applications, psychiatric diseases should be closely monitored, particularly suicidal ideation. Meanwhile, medical personnel should take precautions to guarantee the safety of clinical use and be vigilant for the incidence of AEs not included in the medication instructions