The aim of the study is to evaluate the effectiveness of ozone and betahistine treatments in the treatment of tinnitus. Sixty-eight patients were enrolled in this randomized, prospective controlled study. The ozone group consisted of 27, betahistine group consisted of 26 and control group consisted of 15 patients. The patients in ozone group received 10 sessions of ozone treatment via major autohemotherapy. Betahistine group received 48 mg/day betahistine tablets per oral for 3 months duration. The control group was followed up without any treatment given. The evaluation of tinnitus was made by tinnitus loudness and tinnitus handicap inventory (THI). The changes in findings from baseline to 3rd and 6th months were assessed, and the group results were compared. Comparison of the initial mean tinnitus loudness and 3 and 6 months after treatment in each of the three groups did not reveal a significant difference. The comparison between the groups in terms of the improvement of tinnitus loudness was not significant (p = 0.821). Comparison of the initial mean THI and 3 and 6 months after treatment revealed a significant difference in ozone and betahistine groups but not in the control group. When the delta (Delta) THI (the change of mean THI between the initial and 6th month) was compared between the groups, there was no significant difference. This randomized controlled study investigating the effects of ozone in tinnitus tries to shed light to a new method of treatment in tinnitus. The findings of the study does not provide enough evidence to support ozone and betahistine as a treatment for tinnitus and further research on the subject is necessary.