Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE) are notorious pathogenic multidrug resistant (MDR) bacteria in both hospital and community sectors, and today the first antibacterial drug sulfamethoxazole is ineffective. The monoterpene phenol, thymol was conjugated with seven sulfa drug derivatives individually, adopting the dye-azo synthesis protocol, and conjugates were characterized using spectral analysis techniques such as, UV, FTIR, MS, HPLC, ¹ H NMR, ¹³ C NMR and SEM. Conjugates were assessed for antibacterial activity in vitro and in silico ; the zone of inhibition, MIC and MBC values of each conjugate were determined against isolated MRSA and VRE strains from clinical samples. As 3-dimentional structures of dihydropteroate synthases (DHPSs) of targeted bacteria are not available in protein database, homology models of DHPS enzymes of both bacteria were generated and validated by Ramachandran plots. Seven conjugates were used as ligands in molecular docking against MRSA-DHPS and VRE-DHPS. Additionally bioinformatics tools, PASS prediction, Lipinski rules of five, computational LD ₅₀ value, toxicity class, HOMO, LUMO and EPS plots were carried out to assess standard drug-likeliness properties of conjugates. Zone size inhibition of the conjugate, 4b (thymol + sulfadiazine) against MRSA and VRE strains on agar plates were 20 and 40 μg/mL as the lowest MIC and MBC values, respectively; while the reference antibiotic ampicillin had the lowest MIC and MBC values at 80 to 180 μg/mL. In vitro host-toxicity testing was carried out with cultured human-lymphocytes from umbilical cord blood, and 4b was broadly non-toxic to human cells at 15,000 mg/L. Thus, 4b could be promoted a newer antibacterial, against gruesome MDR bacteria.