Nanoclays may enter human body through various routes such as through the respiratory and gastrointestinal tract, skin, blood, etc. There is dearth of such studies evaluating the interaction of clay nanoparticles with human cells. In particular, the interaction of proteins and nucleic acids with nanoparticles of different aspect ratio remains a domain that is very poorly probed and understood. In the present study, we address the issue of cytotoxicity and antimicrobial attributes of two distinct nanoclay platelets namely, laponite (diameter = 25 nm and thickness = 1 nm) and montmorillonite (MMT, diameter = 300 nm and thickness = 1 nm), having different aspect ratio (25:1 vs 300:1). Cytotoxicity was assessed in both prokatyotes: Escherichia coli, eukaryotes-human embryonic kidney (HEK), and cervical cancer SiHa cell lines, and a comparative size-based analysis of the toxicity were made at different exposure time points by MTT assay. The antimicrobial activity of the nanoclays was evaluated by disc diffusion method (Kirbey-Bauer protocol). Laponite exhibited maximum efficacy as an antimicrobial agent against E. coli. Comparatively smaller size laponite could preferentially enter the cells, leading to relatively wider or larger zone of inhibition. On contradictory; laponite showed 74.67 % survival while MMT showed 89.02 % survival in eukaryotic cells at 0.00001 % (w/v) concentration. In summary, both MMT and laponite indicated cytotoxicity at 0.05 % concentration within 24 h of exposure on HEK and cervical cancer (SiHa) cell lines. The toxicity was possibly dependent on size, aspect ratio, and concentration.