Helicobacter pylori, a spiral-shaped, gram-negative bacterium, is a major causative agent of gastric diseases. Its ability to form biofilms contributes to antibiotic resistance and treatment failure, posing challenges in high-prevalence regions like Vietnam. This in vitro study evaluated the antibiotic resistance patterns of H. pylori biofilms using the Etest method for amoxicillin, clarithromycin, and levofloxacin. The efficacy of curcumin in inhibiting biofilm formation was assessed at concentrations ranging from 1 to 64 μg/mL using a microtiter plate assay. A high prevalence of biofilm formation (92.3%) was observed. Biofilm-forming strains exhibited elevated resistance rates to amoxicillin (97.9%) and clarithromycin (93.8%). Curcumin demonstrated dose-dependent inhibition of biofilm formation, with concentrations ≥16 μg/mL inhibiting 96% of tested strains. Exposure to 16 μg/mL curcumin reduced the minimum inhibitory concentrations (MICs) of amoxicillin and clarithromycin. The findings highlight biofilm formation’s role in H. pylori antibiotic resistance and curcumin’s potential in combating biofilm-associated infections and mitigating resistance. Curcumin may enhance amoxicillin and clarithromycin efficacy by inhibiting biofilm formation and potentially reversing resistance mechanisms. This study highlights not only curcumin’s efficacy in inhibiting biofilm formation but also its role in enhancing the susceptibility of H. pylori to antibiotics, specifically amoxicillin and clarithromycin, suggesting its potential as an adjunct therapy. Further research is needed to explore curcumin’s clinical applications as an adjunct therapy.