The periodontal pocket provides a suitable environment for bacterial accumulation and growth which results in ultimately tooth loss. The clinical efficacy of current therapy for periodontal pocket is low because the flushing actions within the mouth causes to rapid clearance of the solution. The antioxidant and anti-inflammatory effects of atorvastatin (ATV) can facilitate healing process of periodontal diseases. The aim of this study was to develop in situ gel formulation containing ATV-loaded polycaprolactone nanoparticles (PCL-NPs). PCL NPs were prepared by nanoprecipitation method. The NPs had spherical shape with a particle size range of 176-329 nm. They showed 59% encapsulation efficiency and prolonged release profile. In order to increase the mucoadhesive properties of the formulation and the residence time of the drug at the site of action, NPs were incorporated to in situ gel to provide a combination therapy. In situ gel formulation was prepared by cold method and characterized in terms of pH, gelation temperature and time, viscosity, syringeability, and rheological behaviours. In vitro release studies revealed that in situ gel formulation remarkably extend the release time of ATV and mathematical release kinetic modelling shows formulations can fit multiple models. The overall findings indicated that the combination therapy strategy of locally administration of in situ gel containing ATV-loaded polycaprolactone nanoparticles to periodontal pockets is a promising and innovative approach.