Previous studies have reported inconsistent associations between low-carbohydrate diets (LCDs) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCDs in cardiometabolic health. We investigated the cross-sectional associations between LCDs and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasizing unsaturated fat, plant protein, and less low-quality carbohydrates), and unhealthy (emphasizing saturated fat, animal protein, and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein, and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34,785 participants aged 18-85 years were included. After adjusting for covariates including body mass index, healthy LCD was associated with lower levels of insulin, homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), and triglycerides, and higher levels of high-density lipoprotein cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of -5.91, -6.16, -9.13, -9.71, and 7.60 (all Ptrend < 0.001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP, and low-density lipoprotein cholesterol (all Ptrend < 0.001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.