To detect the change during coral–dinoflagellate endosymbiosis establishment, we compared transcriptome data derived from free-living and symbiotic Durusdinium, a coral symbiont genus. We detected differentially expressed genes (DEGs) using two statistical methods (edgeR using raw read data and the Student’s t-test using bootstrap resampling read data) and detected 1214 DEGs between the symbiotic and free-living states, which we subjected to gene ontology (GO) analysis. Based on the representative GO terms and 50 DEGs with low false discovery rates, changes in Durusdinium during endosymbiosis were predicted. The expression of genes related to heat-shock proteins and microtubule-related proteins tended to decrease, and those of photosynthesis genes tended to increase. In addition, a phylogenetic analysis of dapdiamide A (antibiotics) synthase, which was upregulated among the 50 DEGs, confirmed that two genera in the Symbiodiniaceae family, Durusdinium and Symbiodinium, retain dapdiamide A synthase. This antibiotic synthase-related gene may contribute to the high stress tolerance documented in Durusdinium species, and its increased expression during endosymbiosis suggests increased antibacterial activity within the symbiotic complex.