Aim: The aim of this clinical study is to evaluate the effect of Ozone therapy versus the natural healing process on pain perception and the healing at the palatal wound in patients with mucogingival defects after harvesting of free gingival graft (FGG). Methodology: The study included 20 patients in need for FGG surgery for correction of mucogingival defects. Patients were randomly assigned into two equal groups; ozone therapy group (group I; OT) and (control group ; group II)) Periodontal dressing group. Evaluation of the postoperative pain after FGG harvest for both groups was recorded using the visual analogue scale (1-10) for a period of 7 days as primary outcome. While the post-surgical evaluation; the number of analgesic tablets, the palatal wound healing and complete re-epithelialization were defined as secondary outcomes. Results: Group I (OT); showed significant lower VAS score at day 3 and day 7 compared to control group. While group II; significant reduction in VAS score at days 21(SD= 0.3) and 28. Wound healing was evaluated using Landry's healing index, where group I; showed significantly higher healing index scores at days 7 (p<0.001) and 14 (p<0.001) compared to the control group. Conclusion: Ozone therapy produce more significant pain reduction at day 3 and day 7, compared to control sites. Gaseous ozone application to the palatal donor wound, induced complete epithelialization after two weeks and accelerated the healing process compared to control sites.