Microencapsulation is a tremendous technique that permits a compound to be included inside a microstructured system for several objectives including protection and sustained drug delivery. In our study, we prepared mucoadhesive microspheres of Metformin hydrochloride (MET) by ionotropic gelation approach using sodium alginate and calcium chloride as a cross-linker. Three natural polysaccharide copolymers e.g. Okra gum (OKG), Gellan gum (GLG), and Hydroxypropyl methylcellulose (HPMC) were added to alginate in a ratio of 1:1 to investigate their effect on mucoadhesion feature, drug encapsulation efficacy (EE %), and in-vitro drug release. Physical characterizations such as FTIR, XRD, DSC, particle size, and SEM were performed on the prepared microspheres. Ex-vivo mucoadhesive property of the three tested microspheres was investigated using goat intestinal tissue. MET-loaded OKG-alginate microspheres (ALG-OKG) displayed a higher EE% (90 ± 3.28%), more sustained release profile over 10 hours, and better adhesion to goat intestinal mucosa compared with the other microspheres using ALG-GLG or ALG-HPMC blend. Thus, the addition of isolated OKG to sodium alginate was manifested as a prospective controlled drug release polymer-blend in the formulation of sustained-release MET-ionically gelled microspheres for oral administration with expected enhanced bioavailability and better patient compliance due to a decreased dosage interval.