Background: The aim of this study is to comparatively evaluate the efficacy of dehydrated human chorion membrane with and without 2% Metronidazole gel in periodontal pocket therapy in patients with moderate to severe periodontitis. Methods: 40 patients were recruited for the study and were divided into 2 groups of 20 patients each. The clinical parameters assessed were plaque index, gingival index, pocket probing depth and clinical attachment loss. The clinical indices were assessed at baseline, 1 month and 3 months and pocket probing depth and clinical attachment loss were assessed at baseline and 3 months postoperatively. Surgical therapy involved open flap debridement for both groups followed by placement of chorion membrane in Group 1 and placement of chorion membrane with application of 2% metronidazole gel on the flap side of the membrane in Group 2. Results: For all the clinical parameters assessed, highly significant (p<0.01) reduction was observed with respect to the plaque and gingival index scores within the group. Intergroup comparison, however, showed no significant difference. Pocket probing depth and clinical attachment loss showed highly significant (p<0.01) improvement from baseline to 3 months within the groups as well as between the two groups. However, Group 2 (chorion membrane with 2% metronidazole gel) showed a larger effect size than did Group 1 (chorion membrane alone). Conclusion: The results establish that although both treatment modalities i.e., chorion membrane alone or in conjunction with 2% metronidazole gel yielded good results, the latter proved to be more effective and can be promising for the treatment of periodontal pockets in patients with chronic periodontitis.