Meclizine Hydrochloride (MCZ) is an effective antihistamine for the prevention and treatment of nausea and vomiting, with low oral bioavailability (about 30 to 40%) due to low water solubility. The purpose of the current study was to develop and characterize a thermo-responsive nasal in-situ gel for MCZ. To enhance the solubility of MCZ, an inclusion complex with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) was prepared and characterized. The prepared complex was utilized in the preparation of thermosensitive in situ gels using the cold method. Twelve formulations were developed by employing various concentrations of Poloxamer 407, either alone or in combination with Poloxamer 188. Additionally, hydroxypropyl methylcellulose K4M (HPMC K4M) was incorporated as a mucoadhesive polymer. The prepared formulations were characterized by their appearance, pH value, gelation temperature, mucoadhesive force, gel strength, drug content, and drug release rate. The results showed that as the concentration of poloxamer 188 and HPMC K4M were increased, there was a decrease in gelation temperature, an increase in mucoadhesive strength, and a decrease in the percent drug released. The in-situ gel formulation (F9) with 19 % P407, 3 % P188 and 0.5% HPMC K4M was identified as the optimum formula with gelation temperature of (32.62±0.1 °C), pH value (6.13±0.05), gel strength (39.3 ±0.57 sec), mucoadhesive force (3389.30±0.46 dyne/cm²), and in-vitro drug release of (75.7%) over 6 hours by non-Fickian diffusion mechanism. Owing to these properties the prepared formulation may be used as an effective nasal delivery system for management of nausea and vomiting.