The increase in drug-resistant strains poses a severe challenge for Helicobacter pylori (Hp) treatment, and the failure of traditional triple or bismuth quadruple therapy makes it difficult to eradicate Hp. Tailored therapies should be expanded, and traditional Chinese medicine (TCM) may provide the potential regimen. The aim of the present study is to systematically compare TCM-based therapy (TCM combined with Western medicine) and Western medicine as a rescue therapy for Hp re-eradication. Studies through June 12, 2021, with keywords “Helicobacter pylori,” “medicine, Chinese traditional,” or “rescue treatment” and their related expressions were retrieved from PubMed, SinoMed, China National Knowledge Infrastructure, and Wanfang databases. Randomized clinical trials based on PICOS (population, intervention, comparators, outcomes, and study design) eligibility criteria that evaluated the efficacy and safety of integrated therapy on Hp re-eradication were included. The extracted contents included the demographic data of the participants, specific treatment measures, and the results of outcome indicators and safety indicators. Review Manager 5.3 software was used to perform this meta-analysis. Outcome measures including the HP re-eradication rate, symptom remission rate, and adverse effects were seriously analyzed. Under the guide of PRISMA, 18 studies were finally included. Pooled results showed significant differences in eradication rate between integrated and Western medicine therapy in intention-to-treat (ITT) analysis (OR = 2.21, 95% CI: (1.74, 2.81), P < 0.01 ). Symptom remission is higher in the administration of integrated therapy than in the administration of Western medicine therapy (OR = 2.45, 95% CI: (1.78, 3.37), P < 0.01 ). It is also indicated that integrated therapy showed significantly less adverse effects (OR = 0.60, 95% CI: (0.42, 0.84), P < 0.01 . In conclusion, compared with Western medicine therapy, integrated therapy yields a higher eradication rate and acceptable safety profiles.