We conducted this cross-sectional population study with a healthy multi-ethnic urban population (n = 577) in Malaysia, combining nutritional assessments with cardiometabolic biomarkers defined by lipid, atherogenic lipoproteins, inflammation and insulin resistance. We found diametrically opposing associations of carbohydrate (246·6 ± 57·7 g, 54·3 ± 6·5%-TEI) and fat (total = 64·5 ± 19·8 g, 31·6 ± 5·5%-TEI; saturated fat = 14·1 ± 2·7%-TEI) intakes as regards waist circumference, HDL-C, blood pressure, glucose, insulin and HOMA2-IR as well as the large-LDL and large-HDL lipoprotein particles. Diets were then differentiated into either low fat (LF, <30% TEI or <50 g) or high fat (HF, >35% TEI or >70 g) and low carbohydrate (LC, <210 g) or high carbohydrate (HC, >285 g) which yielded LFLC, LFHC, HFLC and HFHC groupings. Cardiometabolic biomarkers were not significantly different (P > 0.05) between LFLC and HFLC groups. LFLC had significantly higher large-LDL particle concentrations compared to HFHC. HOMA-IR2 was significantly higher with HFHC (1·91 ± 1·85, P < 0·001) versus other fat-carbohydrate combinations (LFLC = 1·34 ± 1·07, HFLC = 1·41 ± 1·07; LFHC = 1·31 ± 0·93). After co-variate adjustment, odds of having HOMA2-IR >1.7 in the HFHC group was 2.43 (95% CI: 1·03, 5·72) times more compared to LFLC while odds of having large-LDL <450 nmol/L in the HFHC group was 1.91 (95% CI: 1·06, 3·44) more compared to latter group. Our data suggests that a HFHC dietary combination in Malaysian adults is associated with significant impact on lipoprotein particles and insulin resistance.