Recurrent aphthous ulceration or recurrent aphthous stomatitis is one of the most debilitating and painful oral mucosal disease. This disease entity has no specific cause to occur and no proper laboratory procedures are present to elicit the diagnosis. The treatment options are largely palliative and aimed at reducing symptoms thereby improving patient's oral condition. In the present study the subjects witnessed alleviation of clinical symptoms related to the aphthous ulceration. The aim of the study was to explore the effectiveness of ozonated oil in the treatment of recurrent aphthous ulcer and to compare with sessame oil in order to analyse the effectiveness between the two topical oil medications. A single-blinded placebo-controlled trial comprising of 30 subjects with recurrent aphthous ulcers were divided into Group 1, Group 2 and Group 3 with 10 subjects in each group was performed. Patients in Group 1 received ozonated oil, Group 2 received sesame oil and Group 3 received placebo. Treatment response was assessed by measures of pain reduction, ulcer duration on 2(nd), 4(th) and 6(th) day. Data were analyzed using Wilcokson signed rank test and Friedman test. Participants treated with ozonated oil showed significant reduction in ulcer size, erythema and also alleviated the ulcer pain on 4(th) day of evaluation when compared to sesame oil and placebo group. On 6(th) day subjects treated with ozonated oil and sesame oil showed significant reduction in ulcer size and erythema. No significant difference was observed in placebo group when compared with other two groups on subsequent 2(nd), 4(th) and 6(th) day of evaluation. Ozonated oil and sessame oil, both showed similar effectiveness in relieving the ulcer pain. Ozone with its wide variety of inherent properties has proven to be choice of treatment in completely relieving the ulcer pain and ulcer size when compared with that of its counter medication (i.e. sesame oil).Therefore the results obtained in the present study forecast ozone to be used as a novel treatment approach in recurrent aphthous ulcers.