Studies on longitudinal associations between diet quality and lipid and amino acid metabolism in children and adolescents are limited. We studied associations between diet quality and serum markers of lipid and amino acid metabolism in the Physical Activity and Nutrition in Children (PANIC) study. These analyses included 403 children aged 6–9 years at baseline, 360 re-examined two years later at age 9–11 years, and 219 eight years later at age 15–17 years. Food intake was recorded over four days, and diet quality assessed using the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, and lipoprotein particle sizes were analyzed via nuclear magnetic resonance spectroscopy. Linear mixed-effects models, adjusted for sex, age, body fat percentage, pubertal stage, and physical activity, were used to analyze the associations. Better diet quality was linked to increased serum polyunsaturated fatty acids and reduced saturated and monounsaturated fatty acids, alanine and very low-density lipoprotein (VLDL) particle size. Consuming more vegetables, fruits, berries, vegetable oils and margarine with at least 60% fat, fish, and whole grains associated with higher serum polyunsaturated fatty acids and lower saturated fatty acids and smaller VLDL particles. Conversely, consuming higher-fat dairy products and sugary products associated with higher saturated and monounsaturated fatty acids, branched-chain and aromatic amino acids, and larger VLDL particles. A diet rich in fruits, vegetables, unsaturated fats, and fiber, with reduced processed meat and sugar consumption, promotes favorable metabolic changes relevant to cardiometabolic health.