This paper investigates the impact of natural change in salinity on the morphological plasticity of diatom frustules. In particular, this study uses as an example the highly saline lagoons of the Coorong wetlands in South Australia. These wetlands have been strongly impacted by the drought in South Australia (2004–2010) which has resulted in a salinity gradient of 40 to 134 psu along the wetlands. In this framework, the impact of some environmental variables (i.e., dissolved oxygen, pH, turbidity, salinity, temperature and nutrients) was investigated on the nanoscale features characterizing the cell wall of two diatom species, Cocconeis placentula Ehrenberg and C. pinnata Gregory. The results suggest that not only salinity, but also nutrient concentration play a significant role in the morphological plasticity of the frustule of these two diatom species. It is proposed that the morphological plasticity of the diatom frustules is species-specific and related to their immediate surrounding environmental conditions.