Abstract : The study aimed to compare the effectiveness of a combination of amoxicillin 500 mg and metronidazole 400 mg tablets with a combination of ofloxacin 200 mg + ornidazole 500 mg in enhancing the clinical response to non-surgical treatment of periodontitis. The study sample comprised 20 cases of periodontitis involving male and female patients aged between 16 and 53 years. The periodontitis cases in the sample were divided into two main groups based on the treatment methods employed - one group treated with ofloxacin and ornidazole, and the other group with amoxicillin and metronidazole. Each patient underwent one-hour sessions of scaling and root planing. Subsequently, patients in the first group received Ornidacin (ofloxacin 200 mg and ornidazole 500 mg), while patients in the second group were administered conservative treatment with amoxicillin 500 mg thrice daily and metronidazole 500 mg tablets thrice daily, over a period of 7 consecutive days.. Patients were asked to visit the Department of Periodontology after 1, 2, and 3 months for evaluation of clinical parameters by another researcher, and for supportive treatment. The study findings indicated that the effectiveness of both treatments was nearly comparable, with a slight edge observed for the first group. Moreover, patient compliance slightly favored the group receiving ofloxacin and ornidazole. In conclusion, both treatments exhibited similar efficacy, with no significant variance in adverse drug reactions. Patient compliance was noted to be higher in the group receiving the combination of ofloxacin and ornidazole compared to the amoxicillin and metronidazole combination.