Aim: The aim of the novel study was to check the efficacy of a locally applied 2%w/w nanoemulgel (NEG) of Ketoprofen (KP) in preventing the periodontitis, and was also checked NEG without KP to ensure the effect of eugenol in NEG as an oil phase.

Design: For experimentally induced periodontitis, sterile silk ligatures (3/0) were placed around the crevices of the first left lower molar teeth of the male Wistar rats. During 8 weeks, all rats were fed with 10%w/v sucrose solution. The experimental assessment was carried out at 11 d after treatment of experimental periodontal disease (EPD) rats by various clinical parameters like gingival index (GI), tooth mobility (TM), alveolar bone loss (ABL), histological analysis, detection of TNF-α, and IL-1β in gingival tissue by ELISA and the roughness were measured by atomic force microscopy (AFM) in tapping modes.

Results: After treatment, comparison studies with EPD were performed. NEG loaded with KP prevents significantly (p < 0.05) various parameters (GI, TM, and ABL), which were responsible for periodontitis. The histopathology of the periodontium showed that Group 3 (NEG loaded with KP) had a more significant reduction in inflammatory cell infiltration, alveolar bones resorption, and cementum (p < 0.05). In the topographical images, significant reduction in roughness of NEG loaded with KP was observed in comparison with EPD without treatment.

Conclusion: The study revealed the great synergistic potential of the combined NEG of an anti-inflammatory drug KP along with eugenol as the oil phase, which have potential antibacterial, analgesic, and anesthetic properties to combat periodontal disease.