Recent reports of natural human infection by Plasmodium cynomolgi indicate the increased risk of zoonotic transmission by this simian parasite. The P. cynomolgi Duffy binding protein 2 (PcDBP2) has a potential role in the invasion pathway of host erythrocytes, and it is a possible vaccine candidate against cynomolgi malaria. This study investigates the genetic diversity, haplotypes, and natural selection of PcDBP2 region II from isolates collected from wild macaques in Peninsular Malaysia. Blood samples from 50 P. cynomolgi-infected wild macaques were used in the study. Genomic DNA extracted from the blood samples was used as template for PCR amplification of the PcDBP2 region II. The amplicons were cloned into a plasmid vector and sequenced. MEGA X and DnaSP ver.6.12.03 programmes were used to analyse the DNA sequences. A genealogical relationship of PcDBP2 region II were determined using haplotype network tree on NETWORK ver.10.2. Result showed high genetic diversity (ð = 0.017 ± 0.002; Hd = 1.000 ± 0.001) of the PcDBP2 region II. The Z-test indicates a purifying selection, with population expansion as shown in Tajima’s D analysis. A total of 146 haplotypes of PcDBP2 region II were observed. Phylogenetic tree analysis showed that these haplotypes were grouped into three allelic types (136 for Strain B type, 9 for Berok type, and 1 recombinant type). In the haplotype network, PcDBP2 region II revealed no geographical groupings but was divided into two distinct clusters.