Studies indicate a strong correlation between the length and degree of alcohol and tobacco use and the risk of oral cancer (OC). However, there has been debate concerning the usage of mouthwashes and associated higher risk of OC for many years. The purpose of this study was to gain insight into how using mouthwash influenced the risk of OC. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used when searching the PubMed/MEDLINE, Scopus, and Web of Science databases. Observational studies that addressed the relationship between mouthwash use and OC and involved adult or older adult populations were included. The Newcastle-Ottawa Scale was employed to check the methodological quality, and random effects meta-analysis, along with other subgroup analyses and meta-regression, were utilized to synthesize quantitative data. Out of 5,132 papers identified, 15 case-control studies comprising 6,515 cases and 17,037 controls were included in the review. Seventeen effect measures from these 15 studies were included in the meta-analysis. For individuals who used mouthwash three or more times a day, the pooled OR for OC was 1.00 (95% CI: 0.79-1.26; n = 17 studies). Among those who had used mouthwash for more than 40 years, the OR was 1.30 (95% CI: 1.58-4.82; p = 0.05; n = 2 studies). Some studies suggest that frequent mouthwash use may increase the risk of OC. Given the biological plausibility of this link, we exercise caution in interpreting these findings. It is important to note the limited research on the frequency and duration of mouthwash use. Thus, for the strengthening of the evidence for a possible dose-response effect of mouthwashes on OC risk, we suggest that future research should be focused on the frequency, duration, and substance of mouthwashes in depth.