The aim of the present study was to evaluate the impact of adjunctive systemic Moxifloxacin compared to the use of adjunctive systemic amoxicillin/metronidazole combination, a Well- established regimen, and scaling and root planning (SRP) alone on clinical parameters and GCF MMP-8 levels over 6 months periods in patients with severe chronic periodontitis . Subjects and methods: Thirty patients (20 males and 10 females) with age ranges from 35 to 55 year old were divided into three groups, group one included 10 patients treated with SRP plus Moxifloxacin while group two included 10 patients treated with SRP plus amoxicillin \ metronidazole and group three included 10 patients treated with SRP alone GCF samples were collected to measure MMP- 8 levels at base line, 10days, 3 and 6 months. Clinical parameters including plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were assessed at base line, 3 and 6 months. Results: At 1, 3 and 6 months, all clinical parameters in each group significantly decreased when compared to base line. The reduction in PD and improvement of CAL were higher in SRP plus MXF and SRP+amoxill\metronidazole groups compared to SRP alone.GCF MMP-8 levels for SRP +MXF were significantly decreased at 10 days, 3, 6 months compared to other groups. Conclusion: These data suggest adjunctive use of MXF following SRP is beneficial in improving of periodontal parameters and reducing GCF MMP-8 levels for 6 months duration.