Helicobacter pylori (HP) induces localized inflammation in the gastric region and triggers a systemic humoral immune response. Significant correlations have been observed in adult research examining the potential link between HP infection and the neutrophil/lymphocyte ratio (NLR), the mean counts of neutrophils and lymphocytes, as well as interleukins levels, Transforming Growth Factor levels and complement components such as C3 and C4 levels. The optimal course of therapy should ideally be determined based on the results of antibiotic susceptibility testing. However, the implementation of this approach is not viable in many geographical areas. Consequently, therapy largely depends on the expertise of healthcare professionals and the specific cultural sensitivity profiles of each location. This study aimed to assess the correlation between immunological responses (neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR), IL-1β, IL-6, IL-8, IL-10, IL-17, IL-33,IFN-β, and TGF-β) and HP infection, severity categorization, and pre- and post-treatment status with two distinct modalities. The research comprised groups as follows: teenagers aged 12–17 years, pregnant women aged 19-35 years, individuals with chronic diseases (diabetes and hypertension) aged 50-75 years, and youth patients aged 18-45 years, alongside healthy controls. These individuals were infected of HP. The study included a total of 120 patients who tested positive for HP and 120 patients who tested negative for HP. The eradication rate for H. pylori infection was satisfactory using second-line therapies. Standard 5-week sequential therapy seemed more effective (96%) than standard a week therapy (4%), especially if the strains were susceptible to clarithromycin, in relation to NLR and the values of neutrophils and lymphocytes (p > 0.05), as well as cytokines (IL-1, IL-6, IL-8, IL-17, INF-β) and complement components such as C3 and C4 (p > 0.05). Meanwhile, IL-10, IL-33, and TGF did not show a significant correlation (p > 0.05). The current study suggests the importance of these early markers of inflammation in determining the severity of gastric mucosal inflammation in HP-infected patients. The establishment of an effective strategy necessitates the generation of regional data pertaining to the success rates of various therapeutic approaches.