Objectives: Drug reference databases provide information on potential drug-related medical complications in a dental patient. It is important that database entries and recommendations are supported by evidence-based original studies focused on drug-related dental management complications. The aim of this study was to review and identify database drug categories associated with evidence-based drug-related medical complications during dental treatment. Data sources: Relevant publications on adverse drug reactions and dental management complications were thoroughly reviewed from the literature published between July 1975 and July 2019. Method and materials: The drug reference database "Lexicomp Online for Dentistry" was reviewed to identify medications associated with the highest propensity to trigger drug-related dental management complications, and these were correlated with published original studies in PubMed, Embase, and Scopus databases that associated drug actions with dental treatment complications. Results: Fifty-four publications (1.2% of all full-text articles) reported original studies that directly tested drug associations with dental management complications. The cautions in the drug reference database on drug-related dental treatment mainly focused on local anesthetic precaution (P .001), xerostomia (P .001), bleeding (P .001), and a combination of xerostomia and bleeding (P .001). Antipsychotics/antidepressants were mostly associated with local anesthetic complications (80.95%), xerostomia (81.93%), and a combination of xerostomia and bleeding (22.89%). Bleeding complication was associated with anticoagulants (80.00%) and cancer chemotherapeutic agents (59.21%). Conclusions: Similarities exist within and across different drug categories in the database entries on drug-related medical complications in a dental patient. There were a relatively limited number of publications that directly tested the association between drug-related medical complications and dental therapies. Clinical relevance: The most common drug cautions during dental treatment reported in Lexicomp Online for Dentistry were limited to drug-drug interactions with local anesthetic actions, excessive bleeding, xerostomia, or a combination of any of these. These recommendations were supported by limited evidence-based studies. Keywords: bleeding, dental treatment planning, drug effects, medical complications, xerostomia