Background: Early Childhood Caries (ECC) in the earliest stage is preventable. The studies indicate oral bacteria play an important role in pathogenesis of dental caries. According to high prevalence of ECC, alternative therapies should be explored in order to reduce the occurrence of it. Aim: This study aims to assess the effectiveness of a product containing Povidone Iodine 10% and Sodium Fluoride 0.2% as a supplementary intervention for preventing ECC.Materials and Methods: Thirty-seven children aged 4 to 6 year-old were recruited. Maxillary incisors on each side of the mouth were selected either as a test or control group. Early caries detection examinations were conducted using International Caries Detection and Assessment System (ICDAS) clinically and photographically. In a double-blind, placebo-controlled clinical study, a product containing a mixture of Povidone Iodine 10% and Sodium Fluoride 0.2% was applied to the designated incisors of the test group participants. This application was performed every week for a 3-month. The control group participants received a placebo mixture during the same time interval. The caries detection examinations were conducted again after 6 months and the results were compared. The data was analyzed with SPSS V.18, using McNemar test.Results: The incidence of carious lesions increased for the control group while it decreased in the test group (P<0.05( Conclusion: A product containing PI and F can be effective in preventing ECC.