Calcium-dependent protein kinases (CDPKs) serve as crucial calcium sensors in plants, playing key roles in regulating plant growth, development, and stress responses. In this study, a total of 26 Salvia miltiorrhiza CDPK (SmCDPK) genes were identified through genome-wide analysis, which were unevenly distributed across seven chromosomes. Phylogenetic analysis grouped the 26 SmCDPKs into four distinct subfamilies (Ⅰ-Ⅳ), and systematic predictions were conducted for their physicochemical properties, secondary structures, and subcellular localization. Promoter analysis uncovered multiple cis-elements associated with light, phytohormones, and abiotic stress. Transcriptome profiling under 50 and 100 μmol·L^-1 cadmium (Cd) stress demonstrated tissue-specific expression patterns of these SmCDPK genes. Notably, SmCDPK18 was upregulated in both roots and leaves under Cd exposure, suggesting involvement in Cd detoxification and oxidative regulation. In contrast, SmCDPK2, SmCDPK8, and SmCDPK22 were significantly downregulated in roots. These expression patterns were confirmed by quantitative reverse-transcription PCR (qRT-PCR). This study provides insight into the CDPK gene family in S. miltiorrhiza and its potential roles in cadmium stress response, offering valuable theoretical support and key gene resources for future molecular breeding and environmental adaptation studies in medicinal plants.