Periodontitis is a chronic inflammatory that occurs due to increasing number of bacteria within the tooth plaque which produce an inflammatory immunological response. Current study investigates new therapeutic combinations of fluoroquinolones and PPIs for the treatment of periodontitis in diabetic patients. Further, the antimicrobial, antibiofilm, anti-quorum sensing, time-kill kinetics assay, and molecular docking studies were performed. In the antimicrobial analysis, initially, the PPIs and then fluoroquinolones were screened against isolated clinical strains. In the case of Staphylococcus epidermidis, none of the PPIs were able to show any inhibition within the prescribed range (64 µg/mL). However, in the case of Staphylococcus aureus, a nicer inhibition (3.9 µg/mL) was recorded. The ciprofloxacin amongst all fluoroquinolones was the most active and has shown promising inhibition of both Staphylococcus aureus and Staphylococcus epidermidis (MIC 0.24 µg/mL). Upon using a combination with PPI's, a marked decrease in MIC was noticed with omeprazole (MIC 0.12 µg/mL). Also upon the combination with omeprazole, a better MIC (MIC 0.12 µg/mL) against Staphylococcus epidermidis and Staphylococcus aureus (MIC 0.48 µg/mL) was observed. In antiquorum sensing experiments, the PPI's were checked and omeprazole presented a significant inhibitory zone (12mm) against C. Violaceum. In the case of fluoroquinolones, significant inhibition was recorded (16-20 mm). Likewise, a synergistic effect was recorded in the case of PPIs. For time-kill kinetic studies, the ciprofloxacin, levofloxacin, and their combination with PPIs were showing synergistic effects. It was concluded that the fluoroquinolones and PPIs have significant inhibition of isolates and can be used for the treatment of periodontitis in diabetic patients.