The FMDV VP1 protein has different structures which could decrease or increase the immune response. We undertook a meta-analysis to evaluate the protective effect of VP1 on the FMDV. A systematic search of the PubMed, Embase, CNKI and Wan fang DATA was conducted up to April 2020. Experimental studies involving the VP1 protection effect on FMDV were included. Extracted data were analyzed using Rev-Man 5.3 software. Chi-square tests were used to analyze the heterogeneity among the documents. The fixed-effect model was used for meta-analysis to find the combined effect value and 95% confidence interval. Sensitivity analysis was performed on the differences in the combined values of model effects, and the inverted funnel chart method was used to assess the publication bias of the included literature. A total of 12 articles were included for meta-analysis. The results of showed that VP1 had a protective effect on FMDV [MH = -0.66, 95% CI = (−0.75, -0.56), P < 0.00001]. Sensitivity analysis showed that the results were robust. The funnel graph method showed that the published literature had a small publication bias and met the requirements of this study. It is necessary to study the epitopes of VP1 to produce new vaccines. VP1 could protect animals from FMDV attacks. It is necessary to study the VP1 protein and its epitopes and use it as a new vaccine and diagnostic product.