Purpose: This double-blind randomized controlled trial assessed the effect of subgingival ozone (O3, gaseous ozone, HealOzone MK II, KaVo) and/or hydrogen peroxide (H2O2) on the development of peri-implant mucositis. Materials and Methods: Twenty subjects (mean age, 60 ± 7.7 years) with 80 implants (4 implants each) were recruited. First, a 2-week pretrial phase took place to achieve healthy gingiva. Subsequently, partial gum shields were constructed for the experimental area (around the 4 implants); subjects were asked to refrain from brushing in that area by wearing the gum shield. The following treatments were randomly applied (for 60 seconds) to implant sites on days 0, 7, and 14: (1) air (O2) and saline (0.9% NaCl) (control group), (2) O2 and H2O2 (3%), (3) O3 and saline, and (4) O3 and H2O2. Plaque, gingival, and bleeding indices were recorded on days 0, 7, 14, and 21. Results: Significant differences were seen among the treatments (P .01) in plaque (F = 16.68), modified gingival (F = 7.86), and bleeding (F = 18.42) indices. O3 + saline and O3 + H2O2 produced optimum gingival health scores and were equally effective and the most effective in controlling bleeding (mean score = 0.05), while O2 + saline was the least effective (mean score = 0.56). Conclusion: Ozone showed great potential for management of peri-implant mucositis.