Aim: The purpose of the present investigation was to evaluate and compare the efficacy of resorbable collagen-based tetracycline fibers and chlorhexidine chip placement in the treatment of chronic periodontitis. Methods: A split-mouth design was used to conduct this study. Fifty one patients with periodontal pockets ranging from ≥5 mm to ≤7 mm were selected for the study. The treatment sites were randomly divided into the control and experimental groups. All of the selected sites were treated with scaling and root planning, and then collagen-based resorbable tetracycline fibers and chlohexidine chip were placed adjunctively in equal number of experimental sites at the same visit. Baseline and followup measurements in both treatment groups included plaque index, probing pocket depth, and relative attachment level. Results: Although significant clinical benefits were obtained in all the treatment groups, the adjunctive antimicrobial use of chlorhexidine chip demonstrated better results compared to the locally tetracycline fibers over the 3-month observational period. Conclusions: The delivery of both antimicrobial agent’s tetracycline in a collagen Matrix and chlorhexidine chip was found to improve the benefits of scaling and root planing by a larger magnitude in patients with moderate-to-deep pockets.