Helicobacter pyloriis the primary pathogen responsible for causing gastroduodenal ulcers and stomach cancer. The standard treatment forH. pyloritypically involves a combination of antibiotics and acid-reducing medications. However, the recurrence of ulcers is closely linked to the emergence of antibiotic resistance inH. pylori, necessitating the development of alternative drugs. This report focuses on the investigation of artesunate as a potential alternative to reduce antibiotic use and enhance effectiveness againstH. pylori. Unfortunately, commercial artesunate is available in an acid form, which has poor solubility, especially in gastric acid fluid. The aim of this study is to utilize a water-soluble formulation of artesunate called dry emulsion formulation (ADEF) and combine it with amoxicillin to eradicateH. pylori. In vitro studies were conducted to evaluate the activity of ADEF againstH. pyloriand determine its inhibitory concentrations. In addition, pharmacokinetic parameters of orally administered ADEF and native artesunate were investigated in rats for in vivo studies. The results showed that when combined with amoxicillin and pantoprazole, ADEF exhibited effectiveness againstH. pylori. It is worth noting that the solubility of ADEF in gastric acid appears to be a critical factor for achieving successful treatment. Consequently, ADEF could be considered a promising candidate forH. pyloritherapy.