Aim This study aimed to critically appraise the drug-drug interaction (DDI) screening performance of Google Bard (Google AI, Mountain View, California, United States) by comparing it with the authorized Lexicomp® Online™ database (Wolters Kluwer Health, Philadelphia, Pennsylvania, United States). Methods This cross-sectional study was conducted between April 2023 and August 2023, and enrolled 414 prescriptions that had been collected randomly between April 2023 and June 2023. These prescriptions were processed individually by Lexicomp online and Google Bard to screen for DDIs between antimicrobials and other prescribed medications. Results The total number of DDIs based on Lexicomp and Google Bard were 90 and 68, respectively. Cohen's Kappa (κ) values showed that there was a nil to slight agreement between Lexicomp and Google Bard regarding the DDI risk rating (κ=0.01). Regarding the severity rate, there was a slight agreement between them (κ=0.02), but in terms of reliability rate, there was no agreement (κ =-0.02). Conclusion This study unveiled differences between Lexicomp and Google Bard regarding their DDI identification, severity rating, and reliability rates. It is fundamental to consider that both tools have their strengths and weaknesses and, therefore, should not be individually depended on for final clinical decisions. However, Lexicomp can be considered authoritative in screening DDIs, but Google Bard currently lacks the necessary precision and reliability for conducting such screenings.