The alarming prevalence of microplastics (MPs) in personal care products and their inherent presence in animals and humans necessitate the development of alternative experimental approaches to evaluate their cytotoxicity, mechanisms, and long-term effects. Microfluidic bead-jet printed skin organospheres, comprising epidermal and dermal cells, present significant promise in addressing MP research, creating high-throughput and reproducible screening systems. Medium-density bioprinted E18 pregnant mouse fetus epidermal and dermal cell (Epi-Dc) organospheres exhibited fast self-aggregation, migration, and cellular differentiation. Co-culture revealed a size-dependent MP uptake rate, with smaller MPs having higher internalization ratios. The 100 nm MP penetrated the epidermal layer and migrated toward the central region, while the 500 nm MP remained in the peripheral area. Ultraviolet A (UVA)-irradiated MPs also significantly increased oxidative stress, cell apoptosis, and ROS levels via upregulation of oxidative stress-associated genes (SOD, p53, and Bax). Furthermore, vitamin C treatment following MP-UVA irradiation decreased reactive oxygen species levels, while cell viability assay using conventional skin-associated drugs indicate dose- and time-dependent induced cytotoxicity. These results demonstrate the broad applications of Epi-Dc organospheres in skin toxicity evaluation and rapid drug testing.