In plants, the calmodulin (CaM) proteins is an important calcium-binding protein, which play a crucial role in both regulating plant growth and development, as well as in the resistance mechanisms to various biotic and abiotic stresses. However, there is limited knowledge available on the CaM family functions in Solanum pennellii, a wild tomato species utilized as a genetic resource for cultivated tomatoes. In this study, 6 CaM ( SpCaM) and 45 CaM-like ( SpCML) genes from Solanum pennellii were selected for bioinformatics analysis to obtain insights into their phylogenetic relationships, gene structures, conserved motifs, chromosomal locations, and promoters. The results showed that the 6 SpCaM proteins contained 4 EF-hand domains each, and the 45 SpCML proteins had 2-4 EF-hand domains. The 51 CaM and CaM-like genes contained different intron/exon patterns and they were unevenly distributed across the 12 chromosomes of S. pennellii. The results of the analysis of the conserved motifs and promoter cis-regulatory elements also indicated that these proteins were involved in the responses to biotic and abiotic stresses. qRT-PCR analysis indicated that the SpCaM and SpCML genes had broad expression patterns in abiotic stress conditions and with hormone treatments, in different tissues. The findings of this study will be important for further investigations of the calcium signal transduction mechanisms under stress conditions and lay a theoretical foundation for further exploration of the molecular mechanisms of plant resistance.