Objective: The study was conducted to investigate the interplay between genes, nutritional intakes, and biochemical indicators associated with type 2 diabetes mellitus. Methods: A total of 105 employees from the Department of Science and Technology and Taguig City University participated in the study. Under the genomics component, participants were genotyped for selected type 2 diabetes susceptibility single nucleotide polymorphisms (SNPs) in TCF7L2, GLUT4, PPARG, ADIPOQ, and CDKN2A/B.The group was further screened, randomized, and enrolled in a dietary intervention utilizing optimized brown rice and white rice (N = 76; n = 38 per group) for 6 months. Changes in blood glucose levels, anthropometric indices, blood pressures, and cholesterol profile were observed during the intervention. Expression analyses of genes was also performed. Results: Our results have revealed that: 1) the risk ‘C’ allele of CDKN2A/B rs10811661, a type 2 diabetes susceptibility gene-SNP, is highly occurring among Filipinos and that it may be used as a biomarker for type 2 diabetes among this population, 2) consumption of brown rice can result in reduced levels of blood glucose (fasting blood glucose, post-prandiab blood glucose, glycosylated hemoglobin), weight, body mass index, weight circumference, waist-hip ratio, blood pressures, and total cholesterol, 3) the risk ‘C’ allele of CDKN2A/B rs10811661 can negate the lowering effect of brown rice on blood glucose levels and other risk factors, and 4) continuous intake of brown rice for three months can enhance the expression and, thus, the function of TCF7L2, which is the major susceptibility gene of type 2 diabetes to date. Conclusion: This study, which is an initiative of the Food and Nutrition Research Institute of the Philippine Department of Science and Technology, has examined a potential gene-nutrient-disease interrelationship in type 2 diabetes among Filipinos through the science of nutrigenomics. Our results warrant further exploration of the interplay between genes and nutrient intakes involved in the pathophysiology of type 2 diabetes.