The objective of the present work was isolated, evaluated and performed the toxicity studies and results were compared with marketed available synthetic mucoadhesive polymers. In this study, we used four different plant sources, namely Pithecellobium dulce (PD), Prosopis juliflora (PJ), Acacia arabica (AA) and Abelmoschus esculentus (AE). From the plants, isolated water soluble mucoadhesive materials by cold/hot aqueous extraction. The isolated mucoadhesive materials were proved to be safe and free from toxic or adverse effects. The yield value of four species for (PD), (PJ), (AA) and (AE) was 5.49, 4.91, 3.46 and 3.87 % w/w. We evaluated the swollen volumes, moisture sorption capacities, shear, tensile strengths, compatibility, interaction, and studied toxicity studies with a comparison of synthetic mucoadhesive polymer. Results indicate that, the isolated natural mucoadhesive polymers are generally regarded as safe (GRAS) category polymers and higher than the other natural polymers such as sodium alginate and Guar gum.