Introduction: Coronavirus disease 2019 (COVID-19) has become a pandemic with 1771514 cases identified in the world and 70029 cases in Iran until April 12, 2020. The co-prescription of psychotropics with COVID-19 medication is not uncommon. Healthcare providers should be familiar with many Potential Drug-Drug Interactions (DDIs) between COVID-19 therapeutic agents and psychotropic drugs based on cytochrome P450 metabolism. This review comprehensively summarizes the current literature on DDIs between antiretroviral drugs and chloroquine/hydroxychloroquine, and psychotropics, including antidepressants, antipsychotics, mood stabilizers, and anxiolytics. Methods: Medical databases, including Google Scholar, PubMed, Web of Science, and Scopus were searched to identify studies in English with keywords related to psychiatric disorders, medications used in the treatment of psychiatric disorders and COVID-19 medications. Results: There is a great potential for DDIs between psychiatric and COVID-19 medications ranging from interactions that are not clinically apparent (minor) to those that produce life-threatening adverse drug reactions, or loss of treatment efficacy. The majority of interactions are pharmacokinetic interactions via the cytochrome P450 enzyme system. Conclusion: DDIs are a major concern in the comorbidity of psychiatric disorders and COVID-19 infection resulting in the alteration of expected therapeutic outcomes. The risk of toxicity or lack of efficacy may occur due to a higher or lower plasma concentration of medications. However, psychiatric medication can be safely used in combination with COVID-19 pharmacotherapy with either a wise selection of medication with the least possibility of interaction or careful patient monitoring and management.