Background <p>Associations between the overall quality of dietary macronutrients and the odds of hyperlipidemia remain unknown. This study aimed to first investigate the aforementioned associations, applying a novel multidimensional macronutrient quality index (MQI).</p> Methods <p>A large cross-sectional study (2018–2020) was carried out among 14,544 participants aged 18–79 years from the NEC-Biobank cohort (Northeast region, China). Dietary information was collected from a validated 110-item food frequency questionnaire. MQI was calculated based on fat quality index (FQI), protein quality index (PQI), and carbohydrate quality index (CQI). Binary logistic regression models were used to assess the odds ratio (OR) with 95% confidence intervals (CI).</p> Results <p>Higher MQI was associated with significantly reduced odds of hyperlipidemia (OR_{tertile 3 vs. tertile 1} = 0.82, 95% CI: 0.75–0.90; <i>P</i> _trend &lt; 0.001). For MQI’s sub-indices, higher FQI (OR_{tertile 3 vs. tertile 1} = 0.84, 95% CI: 0.77–0.91; <i>P</i> _trend &lt; 0.001) as well as higher PQI (OR_{tertile 3 vs. tertile 1} = 0.86, 95% CI: 0.79–0.94; <i>P</i> _trend &lt; 0.001) were associated with lower odds of hyperlipidemia.</p> Conclusions <p>Our findings suggested that intake of high-quality macronutrients was associated with reduced odds of hyperlipidemia. These findings contribute novel knowledge to the field of nutrition and metabolic diseases, and lay the foundation for future studies.</p> Clinical trial number <p>Not applicable.</p>