Asiaticoside (AS), an active herbal compound isolated from Centella asiatica, has the potential benefit in promoting type I collagen (COL I) synthesis and osteogenic differentiation in human periodontal ligament cells (HPDLCs). However, it has low aqueous solubility which may hamper the bioavailability. Thus, the aim of this study was to develop thermoresponsive in situ gel containing AS/cyclodextrin (CD) complexes. The non-encapsulated formulations consisted of AS/hydroxypropyl β-CD (HPβCD) complexes and encapsulated formulations containing AS loaded sulfobutylether β-CD/chitosan nanoparticles (SBEβCD/CS NPs) were prepared. The appearance, pH and viscosity of all formulations were within the acceptable range. All formulations formed relatively rapid sol-to-gel transition when contacted with simulated salivary fluid at body temperature. Compared to non-encapsulated formulations, in vitro gelation and rheological studies of encapsulated formulations displayed gel formation that remained longer with high mechanical strength. In vitro mucoadhesion and in vitro release studies revealed that nanoencapsulated in situ gel had excellent mucoadhesive property and could release AS in a sustained manner. These formulations exhibited no cytotoxic effects to HPDCLs. The SBEβCD/CS NPs containing low AS content could express the COL I synthesis. Thus, nanoencapsulated platform could serve as a promising carrier to deliver AS for periodontal tissue regeneration.