Background: The objective of this randomized clinical study was to evaluate the effect of systemic administration of moxifloxacin compared to amoxicillin and metronidazole, combined with non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in a 6-month follow-up. Material and Methods: A total of 39 systemically healthy patients with GAgP were evaluated in this randomized clinical trial. Periodontal parameters were recorded at the baseline during the 1 st , 3 rd and 6 th month. Patients received either 400 mg of moxifloxacin per os once daily or 500 mg of metronidazole and 500 mg amoxicillin per os three times daily for 7 days consecutively. Results: No significant differences between groups were found in any parameters at the baseline. Both groups led to a statistically significant decrease in all clinical periodontal parameters compared to the baseline (PI, p <0.001 and GI, PD, BOP, CAL, p<0.01). There were no differences between the 1 st and 3 rd months or the 3 rd and 6 th months for clinical parameters in the groups. Also, no intergroup difference was observed in any parameters at any time, except the gingival index at 6 th months. Conclusions: Systemic administration of moxifloxacin as an adjunct to non-surgical treatment significantly improves clinical outcomes and provides comparable clinical improvement with less adverse events to that of combination of amoxicillin and metronidazole in the treatment of GAgP.