Expiratory droplets and droplet nuclei can be pathogen carriers for airborne diseases. Their transport characteristics were studied in detail in two idealized floor-supply-type ventilation flow patterns: Unidirectional–upward and single-side–floor, using a multiphase numerical model. The model was validated by running interferometric Mie imaging experiments using test droplets with nonvolatile content, which formed droplet nuclei, ultimately, in a class-100 clean-room chamber. By comparing the droplet dispersion and removal characteristics with data of two other ceiling-supply ventilation systems collected from a previous work, deviations from the perfectly mixed ventilation condition were found to exist in various cases to different extent. The unidirectional–upward system was found to be more efficient in removing the smallest droplet nuclei (formed from droplets) by air extraction, but it became less effective for larger droplets and droplet nuclei. Instead, the single-side–floor system was shown to be more favorable in removing these large droplets and droplet nuclei. In the single-side–floor system, the lateral overall dispersion coefficients for the small droplets and nuclei (initial size ) were about an order of magnitude higher than those in the unidirectional–upward system. It indicated that bulk lateral airflow transport in the single-side–floor system was much stronger than the lateral dispersion mechanism induced mainly by air turbulence in the unidirectional–upward system. The time required for the droplets and droplet nuclei to be transported to the exhaust vent or deposition surfaces for removal varied with different ventilation flow patterns. Possible underestimation of exposure level existed if the perfectly mixed condition was assumed. For example, the weak lateral dispersion in the unidirectional ventilation systems made expiratory droplets and droplet nuclei stay at close distance to the source leading to highly nonuniform spatial distributions. The distance between the source and susceptible patients became an additional concern in exposure analysis. Relative significance of the air-extraction removal mechanism was studied. This can have impact to the performance evaluation of filtration and disinfection systems installed in the indoor environment. These findings revealed the need for further development in a risk-assessment model incorporating the effect of different ventilation systems on distributing expiratory droplets and droplet nuclei nonuniformly in various indoor spaces, such as buildings, aircraft cabins, trains, etc.