Aim: The present in-vitro experimental study was undertaken to evaluate and compare the antimicrobial activity of cetirizine, ibuprofen, and tramadol against the micro-organism Enterococcus faecalis. Methods and Material: Three medicaments were selected for the study, cetirizine, ibuprofen, and tramadol. The experimental groups for the test were as follows: Group 1: cetirizine, Group 2: ibuprofen, Group 3: tramadol, and Group 4: Saline. An agar well diffusion test was used to determine the efficacy of the experimental medicaments against E. faecalis (ATCC 29212). The diameter of inhibition zones was measured in millimeters using an inhibition zone measuring scale and the results were recorded. Statistical Analysis: The statistical analysis was done using ANOVA and post hoc analysis. The p-value was set at <0.05. Results: There was a significant difference in the diameter of growth inhibition zones, with the greatest diameter noted for cetirizine followed by ibuprofen, and tramadol. Conclusions: The antimicrobial effectiveness of cetirizine was found to be superior to the other two medicaments (ibuprofen and tramadol).