Peroxisome proliferator-activated receptors (PPARs) and uncoupling proteins (UCPs) are expressed in adipose tissue, where PPARs are nuclear receptors that function as transcription regulators of the expression of UCPs, mitochondria proteins which uncouple protons in exchange of heat released. The PPARα L162V; PPARγ2 C161T; UCP1 -3826A/G; UCP2 45 bp Ins/Del and -866G/A; and UCP3 -55C/T gene polymorphisms have been previously associated with obesity in different populations, but with inconclusive findings. This study was to investigate the prevalence of these gene polymorphisms and their possible association with obesity in a cohort of Malaysian university students in Kuala Lumpur. Random convenience sampling was performed with informed consents and anthropometric measurements were taken. Mouthwash samples were obtained for genomic DNA extraction and genotyping was performed using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism. Out of the 256 subjects (140 males and 116 females), 170 were lean and 86 were overweight/obese. The mutated PPARα L162V; PPARγ2 C161T; UCP1 -3826A/G; UCP2 45 bp Ins/Del and -866G/A; and UCP3 -55C/T allele frequencies were 0.006, 0.36, 0.58, 0.12, 0.56 and 0.34, respectively. This study failed to find significant differences in the anthropometric indicators of obesity (Body Mass Index, Waist-Hip Ratio and Total Body Fat) between the genotypes of all the PPAR and UCP gene variants. Overall, the genotype and allele distributions were also not significantly different between genders and BMI status. In conclusion, overweight/obesity is not prevalent among the Malaysian university students and the PPAR and UCP gene polymorphisms are not associated with obesity.: