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This study aims to meticulously map the bibliometric landscape of drug‐drug interactions (DDIs) in clinical research. This represents the first use of bibliometric analysis to comprehensively highlight the evolutionary trends and core themes in this critical field of pharmacology. An exhaustive bibliometric search was performed within the Web of Science Core Collection, aiming to comprehensively gather literature on DDIs in clinical settings. A combination of sophisticated analytical tools including DIKW, VOSviewer, and Citespace was utilized for an in‐depth exploration of bibliometric patterns and trends. Of the 3421 initially identified articles, 2622 were considered relevant. The analysis revealed a marked escalation in DDIs publications, with a peak observed in 2020. Five principal thematic clusters emerged: Safety and Adverse Reactions, Drug Metabolism and Efficacy, Disease and Drug Treatment, Research Methods and Practices, and Special Populations and Combined Medication. Key insights included the escalating significance of drug metabolism in pharmacokinetics, heightened focus on cardiovascular and antiviral therapeutics, and the advancing frontier of personalized medicine. Additionally, the analysis underscored the necessity for strategic attention to vulnerable populations and innovative methodological approaches. This study calls for the global harmonization of research methods in DDIs clinical investigations, advocating for the integration of personalized medicine paradigms and the implementation of cutting‐edge computational analytics. It highlights the imperative for inclusive and collaborative research approaches to adeptly address the intricate challenges of contemporary pharmacotherapy. [ABSTRACT FROM AUTHOR]