MgO is an attractive choice for carcinogenic cell destruction in photodynamic therapy, as confirmed by manifold analysis. The prime focus of the presented research is to investigate the toxicity caused by morphologically different MgO nanostructures obtained by annealing at various annealing temperatures. Smart (stimuli-responsive) MgO nanomaterials are a very promising class of nanomaterials, and their properties can be controlled by altering their size, morphology, or other relevant characteristics. The samples investigated here were grown by the co-precipitation technique. Toxicity-dependent parameters were assessed in a HeLa cell model after annealing the grown samples at 350 °C, 450 °C, and 550 °C. After the overall characterization, an analysis of toxicity caused by changes in the MgO nanostructure morphology was tested in a HeLa cell model using a neutral red assay and microscopy. The feasibility of using MgO for PDT was assessed. Empirical modelling was applied to corroborate the experimental results obtained from assessing cell viability losses and reactive oxygen species. The results indicate that MgO is an excellent candidate material for medical applications and could be utilized for its potential ability to upgrade conventionally used techniques.