Background: The current knowledge and understanding of Periodontitis shows that the best chance for clinical improvement may be obtained from implementing complementary strategies like the reduction of the bacterial burden, host modulation, and risk factor modification that targets different aspects of the periodontal balance. The reduction of bacterial burden by Scaling and root planing is the cornerstone of treatment and can be augmented by the use of local antimicrobials with or without host modulation. The aim of the present study was to synthesize and evaluate a muco-adhesive hydrogel matrix carrying 1% Metronidazole (a local antimicrobial) and 2% Doxycycline (a host modulating agent) in the treatment of Periodontitis. Methodology: A chitosan based hydrogel containing 1% metronidazole and 2% doxycycline was synthesized and evaluated for Minimum Inhibitory Concentration (MIC). Twenty Periodontitis patients with at least one site of probing pocket depth 5-7 mm were selected and randomly divided in to control and test groups. Full mouth Scaling and root planning was done in all 20 patients at the first visit and the baseline clinical parameters were recorded. Only the test group patients received intra-pocket delivery of the hydrogel containing 1% metronidazole and 2% doxycycline. All Patients were recalled after 14 days and 30 days for assessment of clinical parameters. Results: The Minimum Inhibitory Concentration of the prepared hydrogel against the prime periodontal pathogens, Porphyromonas gingivalis, Tanerella forsythia, Fusobacterium nucleatum, Prevotella intermedia was found to be as low as 0.4?g/ml. Both groups showed a statistically significant decrease in gingival index scores. However, test group patients showed a significantly higher reduction in probing pocket depths and gingival index scores when compared to the control group. There was no significant improvements in clinical attachment levels in both groups. Conclusion: In this study, the prepared hydrogel containing doxycycline and metronidazole showed the potential to be used as a local drug delivery agent as an adjunct to scaling and root planing in the treatment of Periodontitis. However, future studies with larger sample size and longer duration are needed to explore the efficacy of the gel.