Opisthorchis viverrini (OV) infection, which can progress to cholangiocarcinoma (CCA), poses a critical public health challenge. While numerous studies have investigated behavior modification programs aimed at preventing OV and CCA, the effectiveness of these interventions remains inconclusive. This systematic review and meta-analysis sought to synthesize evidence on the efficacy of behavior modification programs, particularly those based on self-efficacy, in preventing OV and CCA. We reviewed experimental and quasi-experimental studies, comprising 2-group comparisons or 1-group pretest-posttest designs, that evaluated health education interventions focused on behavior modification for OV and CCA prevention. Relevant literatures was systematically retrieved from the PubMed, Google Scholar, ThaiJo, and ThaiLis databases. Of 702 identified studies, 13 met the systematic review and meta-analysis inclusion criteria. The analysis assessed the quality of the studies, extracted data, and evaluated the risk of bias. Standardized mean differences were calculated to determine the impact of self-efficacy– based programs on knowledge, self-efficacy, and behavior modification. The results indicated significant post-intervention improvements in all outcomes (P<0.001) despite high heterogeneity in knowledge (I²=76%), self-efficacy (I²=77%), and behavior modification (I²=93%). The experimental group demonstrated significantly more significant improvements in knowledge (mean difference=1.52, 95% confidence interval (CI)=1.36–1.68), self-efficacy (mean difference=1.08, 95% CI=0.90–1.26), and behavior modification (mean difference=1.78, 95% CI=1.63–1.92) compared to the comparison group, with I² values of 74%, 84%, and 92%, respectively. In conclusion, health education programs grounded in self-efficacy principles effectively enhance knowledge, selfefficacy, and behavior modification to prevent OV and CCA. These findings suggest that self-efficacy–based behavior modification programs may also apply to the prevention of other diseases.