A randomized controlled trial evaluated the effectiveness of a personalized nutrition program (PDP) compared to standard dietary advice on cardiometabolic health. The study involved 347 adults aged 41–70 years, with 177 in the PDP group and 170 in the control group. The PDP used individualized data, including postprandial glucose and triglyceride responses, microbiome, and health history, to provide personalized dietary recommendations via an app. The control group followed standard dietary guidelines. The PDP led to significant reductions in triglycerides (-0.13 mmol/l) and improvements in secondary outcomes like body weight, waist circumference, HbA1c, diet quality, and microbiome diversity. However, no significant differences were found in LDL cholesterol, blood pressure, or other biomarkers between groups. The PDP showed greater adherence and effectiveness in improving health outcomes, particularly in highly adherent participants. The study found that personalized nutrition could lead to meaningful improvements in cardiometabolic health, suggesting that tailored dietary advice may be more effective than standard guidelines. No serious adverse events were reported. The results highlight the potential of personalized nutrition programs in enhancing health outcomes through individualized dietary interventions.A randomized controlled trial evaluated the effectiveness of a personalized nutrition program (PDP) compared to standard dietary advice on cardiometabolic health. The study involved 347 adults aged 41–70 years, with 177 in the PDP group and 170 in the control group. The PDP used individualized data, including postprandial glucose and triglyceride responses, microbiome, and health history, to provide personalized dietary recommendations via an app. The control group followed standard dietary guidelines. The PDP led to significant reductions in triglycerides (-0.13 mmol/l) and improvements in secondary outcomes like body weight, waist circumference, HbA1c, diet quality, and microbiome diversity. However, no significant differences were found in LDL cholesterol, blood pressure, or other biomarkers between groups. The PDP showed greater adherence and effectiveness in improving health outcomes, particularly in highly adherent participants. The study found that personalized nutrition could lead to meaningful improvements in cardiometabolic health, suggesting that tailored dietary advice may be more effective than standard guidelines. No serious adverse events were reported. The results highlight the potential of personalized nutrition programs in enhancing health outcomes through individualized dietary interventions.