Mental illnesses pose social, economic, and health burdens worldwide. The increasing health burden and mental diseases pose the need for investigating other potential medications. The present review focuses on psychedelic medications. The Patient/Participant, Intervention, Outcomes, and Studies ([PICOS) protocol and the Preferred Reporting Items for Systematic Reviews (PRISMA) checklist guided the establishment of the inclusion criteria. Two reviewers sought eligible studies in electronic databases, including ProQuest, PubMed, Google Scholar, and Web of Science. A total of 17 articles met the inclusion criteria and were reviewed for the potential therapeutic effects of psychedelics, including 3,4-methylenedioxymethamphetamine (MDMA), Lysergic acid diethylamide (LSD), and psilocybin, in the management of psychiatric illnesses. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the level of certainty of evidence. Psychedelics’ positive therapeutic effects were reported across the 17 articles. The medications provided relief from psychotic experiences, reduced the severity of depression and anxiety, improved PSTD, improved social cognition, and elevated the mood of the participants. However, adverse effects, including increased irritability, insomnia, rumination, and low mood, were reported and posed the need for patient monitoring. Despite the long-term therapeutic benefits, psychedelics produced adverse effects when used to manage psychiatric illnesses. LSD, MDMA, and psilocybin are emerging as potential medications that could improve the overall quality of life, life satisfaction, and well-being of mentally ill patients. Keywords: Psychiatric illness, psychedelics, MDMA, LSD, psilocybin treatment, depressive symptoms, disease severity, and therapeutic outcomes.