The primary goal of periodontal therapy is the alteration of subgingivalbiofilms present on periodontally diseased sites that could be associated with the progressive destruction of the supportive periodontal tissues.Studies evaluating the effect of locally delivered antimicrobials (LDAs)as an adjunctive therapy to periodontal surgery revealed evidence of improved clinical outcomes in terms of the greater PD reduction and/or clinical attachment gain compared to periodontal surgery alone.Therefore, the aim of the present to evaluate the effect of metronidazole-loaded PLGA nanoparticles combined with open flap debridement versus PLGA nanoparticles combined with open flap debridement on gingival inflammation in patients with chronic periodontitis.Split mouth design was applied where each patient presented 2 contalateral sites with PD ≥ 5mm and these sites were randomly assigned to 1 of 2 groups as follows:Group I received OFD with local delivery of 2 ml of metronidazole loaded PLGA nanoparticles gel using a plastic syringe where 1 ml was delivered after debridement and the other 1 ml after suturing.Group II received OFD with local delivery of 2 ml PLGA nanoparticles gel using aplastic syringe where 1 ml was delivered after debridement and the other 1 ml after suturing.The primary outcome in this study was gingival bleeding index andsecondary outcomes were probing depth, clinical attachment level and plaque index assessed at baseline and 2 and 4 month after periodontal surgery. In the present clinical trial, the changes in mean PD and mean CAL values did not differ for all probing sites included in the surgery at baseline, 2 and 4 months post-operatively between the 2 treatment groups. In addition, mean PD and mean CAL scores for ≥ 5mm sites did not differ between the 2 treatment groups 4 months post-operatively. However, the gingival index showed a significant reduction in 2 months and 4 months post-operatively in the MTZ group than the control group.