This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability (p > 0.05). Gene sets associated with inflammatory response (p = 2.94 × 10⁻⁵) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p = 2.94 × 10⁻⁵) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling (p = 3.15 × 10⁻⁴) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response (p = 3 × 10⁻³) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand (RANKL) expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials.