The domain of unknown function (DUF221 domain-containing) proteins regulates various aspects of plant growth, development, responses to abiotic stresses, and hormone transduction pathways. A comprehensive genome-wide analysis was performed in its genome to understand the role of DDP genes (DUF221) in the common bean (Phaseolus vulgaris L.). A total of 12 DDP genes were identified and distributed in 8 chromosomes in the common bean genome. The physical and biochemical characteristics of amino acids, motif and intron-exon structure, and cis-regulatory elements of DDP members were determined. Phylogenetically all PvDDPs were clustered into nine clades, subsequently supported by their gene structure and conserved motifs distribution. The PvDDPs contained various cis-acting elements involved in plant responses to abiotic and various phytohormones stresses. A total of 45 different cisregulatory elements in the putative promoter regions of the PvDDPs were identified. ERE and ABRE were discovered to be present in all PvDDPs, indicating that they may be regulated by ethylene and ABA, both of which are strongly associated with biotic stress response in plant species. Additionally, PvDDPs were targeted by multiple miRNA gene families as well. In this context, the most targeted DDP family members are PvDD10 and PvDDP11. The miRNA target analysis showed that Pvu-miR2594, Pvu-miR169, Pvu-miR2584, Pvu-miR530, Pvu-miR156, and PvumiR2592 target these genes. There is a strong correlation between abiotic stress and PvDDPs expression in both leaf and root tissues. PvDDP11 is the unique and highest upregulated gene with hormone treatment and abiotic stress among all the members. Expression of the PvDDP11 gene indicated a strong correlation with drought and salt stress in the common bean roots and leaves, respectively. In conclusion, this study predicted that the putative DDP genes might help improve abiotic and phytohormone tolerance in common bean.