Domain of unknown function (DUF) is a general term for many uncharacterized domains with two distinct features: relatively conservative amino acid sequence and unknown function of the domain. In the Pfam 35.0 database, 4795 (24%) gene families belong to the DUF type, yet, their functions remain to be explored. This review summarizes the characteristics of the DUF protein families and their functions in regulating plant growth and development, generating responses to biotic and abiotic stress, and other regulatory roles in plant life. Though very limited information is available about these proteins yet, by taking advantage of emerging omics and bioinformatic tools, functional studies of DUF proteins could be utilized in future molecular studies.