In this study, the adsorption behavior of chloral hydrate (CH), a toxic sedative and potential environmental contaminant, on a C₈B₆N₆ fullerene-like nanocluster was systematically investigated using Density Functional Theory (DFT). Geometry optimizations and frequency calculations were performed at the B3LYP/6-31G* level to explore structural, electronic, and thermodynamic properties in both gaseous and aqueous phases. Three adsorption configurations were analyzed to determine the most stable conformer. The calculated adsorption energies were negative for all configurations, confirming the feasibility of the adsorption process. Among them, the B-conformer exhibited the strongest interaction, with adsorption energies of −102.395 kJ/mol in vacuum and −52.510 kJ/mol in water. The relatively moderate adsorption energies (<150 kJ/mol), absence of bond formation in NBO analysis, and minimal structural distortion indicate that the interaction mechanism is predominantly physisorption. Thermodynamic analyses revealed negative ΔH_ad and ΔG_ad values across the temperature range of 298–318 K, confirming that the adsorption process is exothermic and spontaneous, while lower temperatures favor stronger interactions. Frontier molecular orbital (FMO) analysis demonstrated a significant reduction in the band gap of C₈B₆N₆ upon CH adsorption (up to ~52% for the B-conformer), indicating enhanced electronic sensitivity and charge transfer capability. Additionally, adsorption reduced chemical hardness and increased electrophilicity, suggesting improved reactivity and sensing potential. These findings highlight the promising capability of C₈B₆N₆ nanoclusters for chloral hydrate adsorption and detection, offering valuable insights for the design of boron nitride-based nanomaterials in environmental remediation and sensor applications.