Prior studies have yielded mixed findings concerning the association between apolipoprotein E(APOE)-ε4 and serum lipids in patients with Alzheimer’s disease (AD) and healthy individuals. Some studies suggested a relationship between APOEε4 and serum lipids in patients with AD and healthy individuals, whereas others proposed that the APOEε4 allele affects lipids only in patients with AD. Our study aimed to investigate whether APOE alleles have a distinct impact on lipids in AD. We conducted a comprehensive search of the PubMed and Embase databases for all related studies that investigate APOE and serum lipids of AD from the inception to 30 May 2022. Elevated total cholesterol (TC) and low-density lipoprotein (LDL) levels were found in APOEε4 allele carriers compared with non-carriers. No significant differences were found for high-density lipoprotein (HDL) and triglyceride (TG) levels in APOEε4 allele carriers compared to non-carriers. Notably, elevated TC and LDL levels showed considerable heterogeneity between patients with AD and healthy controls. A network meta-analysis did not find a distinct effect of carrying one or two APOEε4 alleles on lipid profiles. Higher TC and LDL levels were found in APOEε4 allele carriers compared with non-carriers, and the difference was more significant in patients with AD than in healthy controls.