Calmodulin (CaM) and calmodulin-like (CML) gene families are important in combating stress conditions in plants. A total of 36 CaMs/CMLs were identified and found to be randomly dispersed over the 11 chromosomes of Citrullus lanatus (watermelon). Domain analysis verified the presence of characteristic four EF-hand domains in ClCaM proteins and 2-4 EF-hand domains in ClCML proteins. Most of the ClCML genes were intron-less, but all the ClCaM had introns. In the promoter region, 11% of the cis -regulatory elements were identified belonging to abiotic stress. Collinearity analysis suggested that the ClCaM/ClCML gene family expanded due to segmental duplications. Synteny analysis of 36 ClCaM/CML exhibited 31 pairs of collinearity with Arabidopsis thaliana . Twelve miRNAs were predicted to target one ClCaM and eleven ClCML genes. Analysis by real time quantitative PCR indicated all genes expressed under abiotic treatments. Among the analysed genes, ClCML1 is the most highly expressed gene, especially under cold stress, suggesting its strong involvement in stress response mechanisms. ClCML5 and ClCML27 showed consistent upregulation under salt and drought stresses, highlighting their potential roles in the salt and drought tolerance mechanism. These findings will facilitate the subsequent experiments in exploring the calcium signalling channel under stress situations and pave the way for further exploration of molecular mechanisms involved in defenses against cold, drought, and salt stress.