Seborrheic dermatitis (SD) is generally treated with topical steroids, antifungals, or both. The aim of this study was to compare the efficacy of sertaconazole 2% cream vs. metronidazole 1% gel in the treatment of seborrheic dermatitis. A group of 156 patients suffering from SD were studied. The patients were randomly divided into two groups. The first group received local sertaconazole 2% cream and they were recommended to use the cream twice a day for 4 weeks. In the control group, thirty patients received metronidazole 1% gel twice a day for four weeks. At the point of referral, and also 2 and 4 weeks after the first visit, the patients were examined by a dermatologist to identify improvement of clinical symptoms. A higher level of satisfaction was observed after 28 days in the sertaconazole group (87.1%) than the metronidazole group (56.4%). Considering its efficacy, safety, and acceptability profiles, sertaconazole 2% cream is a worthwhile alternative to existing antifungal therapies for the treatment of seborrheic dermatitis.