Helicobacter pylori reside in the gastric mucus layer and at the mucus-epithelial cell interface wherein access of antimicrobial drug to the infection site is restricted both from the stomach and from the gastric blood supply. The aim of the present study was to develop pectin or gellan gum blended sodium alginate microspheres in order to eradicate gastric Helicobacter pylori. The percentage drug release and mucoadhesion were decrease on increasing the calcium chloride in the formulation dispersion. Curing time significantly effected encapsulation efficiency and was not affected % drug content, % buoyancy, and particle size and drug release. The efficacy of the optimized formulation was evidenced by absence of amplified bacterial gene in treated stomach tissue of Mongolian gerbils as observed using in polymerase chain reaction. The results demonstrate that the developed formulation of Am has potential to eradicate Helicobacter pylori by targeted and prolonged retention at gastric mucosa.