This article presents case studies illustrating the management of patients with multimorbidity and confirmed Helicobacter pylori infection, who were recommended the Lactobacillus reuteri DSM 17648-based metabiotic. Particular attention is paid to the situations when the standard antibacterial eradication therapy was challenging or impossible due to contraindications, a high risk of side effects, or drug intolerance. The first clinical observation shows a patient treated with terbinafine for onychomycosis, who developed a complication in the form of mild hepatotoxicity. The Lactobacillus reuteri DSM 17648 metabiotic was chosen as an alternative to conventional therapy for the concomitant Helicobacter pylori­-associated gastritis, with good treatment outcomes. The second observation describes a case of drug-induced hepatotoxicity in a patient with liver disease, who received Helicobacter pylori eradication therapy. Due to discontinuation of antibiotics as part of the eradication regimen and introduction of the metabiotic into the treatment plan, the laboratory parameters returned to normal, and Helicobacter pylori eradication was achieved. The third case is a report of toxicoderma in a patient with Helicobacter pylori infection under treatment with bismuth quadruple therapy (BQT). The successful eradication of Helicobacter pylori without adverse events was achieved through replacement of the bismuth drug with the metabiotic. These observations demonstrate practical approaches to personalized therapy that expands patient management options with the introduction of Lactobacillus reuteri DSM 17648 in the therapy regimen when standard treatments are not possible. The options of using Lactobacillus reuteri DSM 17648 in highrisk patients and its potential role in preventing reinfection after treatment are discussed.