Abstract: The present study was aimed at the formulation and evaluation of Buspirone Hydrochloride buccal tablets using Okra gum as a natural mucoadhesive polymer. Buspirone Hydrochloride buccal tablets were prepared by the direct compression method using Okra gum as the natural mucoadhesive polymer. A Quality by Design (QbD)-based Response Surface Methodology (RSM) approach was employed for formulation development and optimization using a randomized Box–Behnken design. The prepared formulations were subjected to preformulation and post-compression evaluation studies.FTIR studies indicated the absence of significant chemical incompatibility between the drug and selected excipients. The powder blends exhibited satisfactory micromeritic properties, with bulk density ranging from 0.419 to 0.438 g/mL, tapped density from 0.512 to 0.552 g/mL, compressibility index from 14.84 to 21.20%, Hausner ratio from 1.17 to 1.27, and angle of repose from 26.0° to 30.5°, indicating suitability for direct compression. The prepared F1–F12 buccal tablets were evaluated for weight variation, thickness, hardness, friability, drug content, disintegration time and swelling index. The tablet weight ranged from 297 to 302 mg, thickness from 3.1 to 3.5 mm, hardness from 3.76 to 4.30 kg/cm², and friability from 0.37 to 0.46%. The drug content ranged from 82.15 to 96.18%, while the disintegration time ranged from 15.8 to 20.1 min. The swelling index of the formulations ranged from 63 to 128%, demonstrating the swelling and hydration ability of Okra gum. In vitro drug release studies were carried out using USP Type II dissolution apparatus in 900 mL of pH 6.8 phosphate buffer at 37 ± 0.5°C for 8 h. All formulations exhibited progressive drug release throughout the study period. Among the formulations, F3 showed the highest cumulative drug release of 97.42% at 8 h, along with a drug content of 96.18% and swelling index of 128%. The observed results indicated that the concentration of Okra gum and other formulation components influenced the swelling and drug-release behavior of the buccal tablets. The selected formulation F3 was subjected to stability studies for 90 days under different storage conditions. The cumulative drug release showed only a gradual change from 97.42% initially to 94.59%, 94.42% and 94.36% after three months under 25°C/60% RH, 30°C/75% RH and 40°C/75% RH conditions, respectively. No appreciable changes were observed during the study period, indicating satisfactory stability of the formulation. The study demonstrated that Okra gum can be used as a natural mucoadhesive polymer in the development of Buspirone Hydrochloride buccal tablets. The developed formulation exhibited satisfactory physicochemical characteristics, swelling behavior and prolonged drug release and may provide a promising approach for buccal delivery of Buspirone Hydrochloride.