The CLE (CLAVATA3/EMBRYO SURROUNDING REGION-related) small peptides constitute a large supergene family in plants and are extensively involved in plant stress responses and the regulation of growth and development. Light, water, gravity, and mechanical trauma play critical roles in maintaining normal plant growth and development; however, there have been no reports as to whether CLE genes are involved in the responses of sesame to these forms of stress. In this study, the CLE gene family in Zhongzhi No. 13 was systematically identified. Stress induction was performed using light and gravity, and the expression patterns in various tissues and organs were analyzed by means of transcriptome sequencing. Concurrently, the water stress response published in the NCBI database was queried and analyzed. The results showed that a total of 12 SiCLE genes exist in the genome of Zhongzhi No. 13, distributed on six chromosomes. Each gene encodes a signal peptide at its N-terminus and a conserved motif at its C-terminus. The majority of SiCLE genes exhibit a single-exon structure. The SiCLE genes encode proteins ranging from 72 to 133 amino acids in length. Most of these proteins are basic, hydrophobic, and unstable. An analysis of promoter cis-acting elements revealed that the majority of SiCLE gene family members harbor response elements associated with light, phytohormones, stress, and growth and development. Transcriptome analysis revealed that SiCLE4, SiCLE5, SiCLE8, and SiCLE10 exhibit differential expression under water stress, light stress, and gravity stress/mechanical damage conditions. These results provide a solid foundation for future investigations aimed at elucidating the biological roles of the CLE gene family in both abiotic stress responses and the regulation of growth and development.