A complex formulation for topical treatment, consisting of melatonin, hyaluronic acid, tetracycline, and metronidazole mixture is proposed as periodontal disease adjunctive treatment. In order to follow the structural aspects of the active mixture, spectrophotometric methods: UV-Vis and fluorescence, have been applied. The results obtained complete our previous studies. By adding metronidazole to the mixture composed of: melatonin, hyaluronic acid, and tetracycline, the conjugated effect of the active compounds, combining antimicrobial action with anti-inflammatory and immunomodulatory effect, is expected to significaly improve supportive therapy in moderate forms of periodontitis.