Receptor activator of the nuclear factor-κB ligand (RANKL) and osteoprotegerin genes (OPG) were identified as susceptible loci for postmenopausal osteoporosis (PMO) in various ethnicities, but neither have been studied in an Arabian population. Hence, the current study aimed to fill this gap. A total of 372 postmenopausal women (174 osteoporosis (OP) and 198 control group (CTRs)) were genotyped for four SNPs: rs2277438A/G and rs9533156T/C (), and rs2073618C/G and rs3102735T/C (). Anthropometrics, bone mineral density, 25(OH)D and several other bone markers were measured. The frequency distribution of the heterozygous CG genotype of rs2073618 () was lower in the OP (36.8%) than in CTRs (47%) (OR: 0.6, 95% CI: 0.3-0.97; = 0.041). No differences in the allelic/genotypic frequencies were detected between the two groups for all other studied SNPs. However, the heterozygous TC genotype of rs3102735 () was associated significantly with lower BMD at the femoral neck in OP subjects ( = 0.04). The homozygous rare CC genotype of rs9533156 () was associated with lower 25(OH)D levels in CTRs ( = 0.032). In contrast, heterozygous AG genotype of rs2277438 () is associated with lower 25(OH)D in the OP group ( = 0.02). Our results suggest that SNPs may impact 25(OH)D levels and that SNP rs2073618A/G is a significant genetic risk factor for PMO Saudi Arabian women.