The study analyses the possibility of using polyhydroxyethyl methacrylate as a material for the slow release of antibiotic in periodontal pockets. The antibiotics examined were tetracycline and metronidazole. The aim of the study was to evaluate the biocompatibility of the material with periodontal tissue and the efficacy of the 2 prepared systems. Two sites were selected in 2 periodontopathic patients who after non-surgical treatment presented pockets measuring 8 and 7 mm. A sheet of pHEMA containing tetracycline was inserted in one and in the other a sheet containing metronidazole: both were left for 8 days in the chosen pockets. At the start and end of treatment PD and GI clinical indices were measured and the DMDx microbiological test was performed to identify Aa of Pg and Pi. The tissue reaction to pHEMA was evaluated using SEM analysis of two samples collected after 8 days of treatment. The microscopic results showed the optimal biocompatibility of both samples. Differences were noted with regard to clinical and microbiological efficacy. It was observed that the sheet of pHEMA containing tetracycline resulted in the disappearance of bleeding and a reduced depth of survey. Moreover, microbiological results showed a significant reduction in Porphyromonas gingivalis. The sheet of pHEMA containing metronidazole showed a lower level of therapeutic efficacy. Although reduced depth was noted, gingival bleeding was persistent and the reduction of bacteria analysed was not significant. In conclusion, the authors confirm the optimal biocompatibility of the material and its easy application, although further research, especially for pHEMA with metronidazole, must be carried out to improve drug kinetics, trying to maintain an effective local concentration throughout treatment.