The aim of this study was to evaluate the influence of 3% ethanol extract of propolis (EEP) on hygiene, gingival and microbiological status of oral cavity in patients with cleft lip and palate treated with fixed orthodontic appliances. The study included forty-one nonsyndromic complete unilateral of bilateral cleft lip and palate subjects with fixed appliance on at least 10 teeth. Twenty-one subjects were instructed to brush their teeth three times a day using toothpaste with propolis. Control group included twenty subjects who were asked to brush their teeth three times a day using a toothpaste without propolis. API, OPI, GI, and supragingival bacterial plaque were taken from each subject twice: baseline and after using the toothpaste for 35 days. The final examinations showed statistically significant decrease in OPI, GI, and the percentage of the Actinomyces spp. and Capnocytophaga spp. compared with baseline in propolis group subjects. The improvement in oral health in these patients confirms antibacterial, anti-inflammatory, and regenerative properties of propolis.