Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30–69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA [ribosomal ribonucleic acid], N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean [SD]=126.0 [17.4] mm Hg) and diastolic BP (DBP [80.7 (10.7) mm Hg]). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA P <0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient [95% CI] per 1 SD pattern score: 2.23 [0.72–3.74] mm Hg) and DBP (1.72 [0.81–2.63] mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate–adjusted linear model P <0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate–adjusted Fisher exact test P <0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.