Helicobacter pylori remains a significant public health concern because of its association with chronic gastric infection, recurrent peptic ulcer disease (PUD), and increasing antimicrobial resistance (AMR). The review also considers socioeconomic inequalities, diagnostic limitations, and challenges in implementing effective eradication programmes. This narrative review synthesizes current evidence on the global and Indian epidemiology of H. pylori-associated PUD, antimicrobial resistance trends, treatment failures, and their implications for public health and healthcare services. Substantial geographical variation in resistance to metronidazole, clarithromycin, levofloxacin, and amoxicillin, particularly in India, has reduced the effectiveness of several empirical eradication regimens. Effective management requires antimicrobial stewardship, susceptibility-guided therapy, post-treatment confirmation of eradication, and equitable access to reliable diagnostic services. Emerging strategies include molecular resistance testing, vonoprazan-based therapies, adjunctive probiotics, evidence-based investigation of plant-derived antimicrobial compounds, urease inhibitors, and vaccine development. Coordinated clinical, diagnostic, public health, and research efforts are essential to reduce treatment failures, unnecessary antibiotic exposure, and the overall burden of H. pylori infection and associated PUD. Keywords: Helicobacter pylori; Peptic ulcer disease; Antimicrobial resistance; Epidemiology; Antimicrobial stewardship