OBJECTIVE: Tramadol is a synthetic opioid widely used in clinical practice to treat moderate to severe pain. While it is considered safer than traditional opioids, growing concerns have emerged regarding its adverse psychological effects. This systematic review examined tramadol-induced psychological side effects, identified risk factors, and evaluated possible underlying mechanisms that might help to guide safer clinical use. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar using the related keywords of tramadol and psychological effects. This review primarily focused on case reports, which were included if they provided detailed accounts of tramadol-induced mental health side-effects. Two independent reviewers screened the studies, and data was extracted on patient demographics, details of tramadol usage, psychological outcomes, and risk factors. The quality of the case reports was assessed using the Joanna Briggs Institute (JBI) scale. RESULTS: The review found that tramadol is associated with a range of psychological symptoms, including manic episodes, hypomania, serotonin syndrome, psychosis, and cognitive impairment. Risk factors included age, pre-existing psychiatric conditions, polydrug use, and prolonged tramadol use. Elderly individuals and those with psychiatric histories were particularly vulnerable. CONCLUSION: Tramadol has the potential to cause serious psychological side effects, prompting cautious prescription, especially in vulnerable populations. Clinicians should closely monitor patients for these adverse effects, and further research is needed to understand the mechanisms involved and to reduce the psychological site-effects resulting from tramadol use.