Objective To explore the relationship between apolipoprotein E (APOE) gene polymorphism and dementia with Lewy bodies (DLB). Methods PubMed, EMBASE, Cochrane library, and CNKI were searched for relevant articles published up to April 2018. The inclusion and exclusion criteria for articles were determined, and the quality of articles was evaluated using the Newcastle-Ottawa Scale. Related data were extracted from high-quality articles and the RevMan 5.3 software was used for statistical analysis. Results Twenty-one articles were included, including 1 178 DLB patients and 6 272 healthy controls. Meta-analysis showed that APOE ε4 was a risk factor for DLB:ε4 vs ε3 (odds ratio[OR]=2.51, 95% confidence interval[CI]:1.87-3.38, P<0.001); ε4 vs ε2 (OR=2.71, 95%CI:1.73-4.26, P=0.007). However, there was no significant relationship between the APOE ε2 and DLB (P>0.05). In the subgroup analysis of the Caucasian population, consistent results were also obtained. Conclusions APOE gene polymorphism is associated with DLB, and APOE ε4 is a risk factor for DLB. There is no significant relationship between APOE ε2 and DLB susceptibility.