Arachidonic acids are metabolized by cytochromes P450 (CYP450) to epoxyeicosatrienoic acids (EETs). EETs have many cardiovascular protective effects such as vasodilation, anti-hypertension, anti-inflammation, lipid-lowering effects, and favorable effects on glucose homeostasis. This study aimed to investigate whether gene polymorphism of cytochrome P450 CYP2C9 and CYP2C19 are related to the risk of hypertension, hyperlipidemia, and diabetes mellitus. Four hundred and eighty patients were enrolled, and single nucleotide polymorphisms for CYP2C9 and CYP2C19 were genotyped. The percentages of patients with hypertension, hyperlipidemia, and diabetes mellitus with CYP2C9 *1/*2, *1/*3, and wild-type (CYP2C9 *1/*1) were similar, and the chi-square (χ2) analysis showed no statistically significant differences between each genotype. Further, no statistically significant differences were observed for the percentages of patients with hypertension, hyperlipidemia, and diabetes mellitus between CYP2C19 genotypes. Subgroup analysis showed that among patients with the wild-type CYP2C9 genotype (CYP2C9*1/*1, N = 297), patients with CYP2C19*1/*2 and *2/*2 genotypes have a significantly higher percentage of hyperlipidemia than those with CYP2C19 *1/*1, *1/*17, and *17/*17 genotypes. Binary logistic regression analysis also suggested that among patients with the wild-type CYP2C9 genotype, the CYP2C19*2 allele was associated with risk of hyperlipidemia (P = 0.027, odds ratio = 2.036; 95% confidence interval = 1.09-3.82). General linear model analysis showed that among our general research population, both CYP2C9 and CYP2C19 had no effect on hyperlipidemia independently, but the interaction between CYP2C9 and CYP2C19 and hyperlipidemia was statistically significant (F = 2.682, P = 0.031). Our study suggests that the association of CYP2C19*2 with hyperlipidemia was specific among patients with the wild-type CYP2C9.