Background: Cellulite is a common disease whose exact mechanism is unknown. This study was aimed to assess the safety and efficacy of an anti-cellulite preparation compared with placebo in a randomized double-blind, right-left comparison clinical trial.Methods: Twelve healthy women aged 22 to 58 years with mild to moderate cellulite on their thighs and buttocks participated in this trial. The anti-cellulite preparation (Three O cream, Pouya Varzan Tejarat Sepahan Co., Iran) and an identical placebo were randomly applied on the right or left thigh and buttock twice a day for 2 months. The mentioned areas were photographed and the circumference, subcutaneous fat thickness, and dermis density and thickness were measured before and after treatment. A satisfaction questionnaire was completed by all volunteers to assess their satisfaction with the efficacy of treatment on each side.Results: There was no significant difference between active and placebo treatment sides in any of measurements. About 90% of participants had an overall satisfaction of 5 and more than 5 based on a 0 to 10 visual analogue scale on the side of anti-cellulite cream. This score was similar on the sides treated with placebo and the active product.Conclusion: Although Three O cream provided more satisfaction in volunteers than placebo, the objective measurements did not show any difference between them.