Carbon dots are emerging carbon-based nanomaterials because of their unique optical properties, high surface area, and surface chelating functional groups. In this work, carbon dots were prepared from jackfruit using a one-step hydrothermal method and used as a sensing layer in an optical electronic nose for the real-time detection of acetone vapor at room temperature. The carbon dots showed blue photoluminescence with excitation-dependent fluorescence emission, excellent photostability, and a quantum yield of 5.2%. Using principal component analysis, the carbon dot-integrated electronic nose was able to distinguish acetone from hexane, ethanol, methanol, and water and between different concentrations of acetone in ethanol and aqueous solutions. From the time-dependent density functional theory calculations, an increase in carbon dot's extinction coefficients in bulk solvents was in a good agreement with the optical electronic nose results. The calculations of interaction energy using density functional theory method illustrated the electronic coupling and interfacial interactions between carbon dots and acetone and other volatile organic compounds. Interestingly, the unique ambipolar properties of carbon dots were computationally demonstrated. Furthermore, the photoluminescence of carbon dots was also exploited for the detection of acetone in aqueous solutions. Based on this work, our jackfruit-derived carbon dots were demonstrated to be versatile sensing materials for acetone in vapor and solution, and the computational methods highlighted the importance of interfacial electronic coupling towards unique sensing properties of carbon dots.