The main aim of drug targeting was to increase the selectivity and efficacy of drugs at the infected site and to reduce the toxicity of biotechnological entities on other parts of the body. In the present study, we selected the triple therapy (amoxicillin, clarithromycin and omeprazole) due to its synergic and additive effects, which could drastically reduce the effective dose required for the complete eradication of Helicobacter pylori and prevent the development of antibiotic resistance. The gliadin nanoparticles (GNP) vis-à-vis lectin-conjugated gliadin nanoparticles (LGNP) of triple therapy were prepared by a desolvation method and evaluated for percent entrapment efficiency, percent yield, in vitro drug release study and mucoadhesion properties of formulations. The maximum percent entrapment efficiency of formulations was in the range of 65-85%. The percent yield of formulation was about 84 +/- 2.68%. The maximum percent cumulative release of all the three drugs from formulations was in the range of 22-76%. The specificity of lectin-conjugated particles was assessed by an in vitro agglutination assay method. The developed formulation was also assessed for in vitro antibacterial study, in vivo clearance efficacy and histopathological evaluation of formulations. In the in vitro antibacterial study, the LGNP with triple therapy showed a 94.83% eradication rate that is 7.4% more than that of GNP with triple therapy (88.28%) and about 16% more than that of the plain triple therapy (P < 0.001). The targeted lectin-conjugated formulations exhibited a superior in vivo clearance efficacy when compared to the non-conjugated formulations and plain drugs.