The present research is designed to evaluate the pharmacokinetic profile, histological evaluation, and stability studies of an orodispersible film (ODF) of tizanidine (TZ) and meloxicam (MX) prepared from a natural polysaccharide, i.e., xanthan gum. In vivo release study of TZ and MX was performed in rabbits and results indicated the better pharmacokinetics parameters and improved the oral bioavailability when compared to the oral aqueous suspension and solution of TZ and MX, respectively. The intermediate stability studies were performed at 30±2°C and 65±5% RH, whereas, the accelerated stability studies were carried out at 40±2°C and 75±5% RH, respectively for the duration of six months and results indicated that the ODF was stable for six months without any substantial difference in essential physico-chemical parameters, mechanical attributes, and morphological constraints. The toxicity profile of ODF was determined through histopathology of vital organs after administering the ODF to the rabbits. Histopathology revealed that the tissues of all vital organs are normal and did not exhibit any abnormalities, lesions, or hemorrhage. Therefore, the ODF prepared from xanthan gum exhibited a non-toxic and stable formulation with a better pharmacokinetics profile of MX and TZ.