Manipulating matter by strong coupling to the vacuum field has attracted intensive interests over the last decade. In particular, vibrational strong coupling (VSC) has shown great potential for modifying ground state properties in solution chemistry and biochemical processes. In this work, the effect of VSC of water on the melting behaviour of ds-DNA, an important biophysical process, is explored. Several experimental conditions, including the concentration of ds-DNA, cavity profile, solution environment, as well as thermal annealing treatment, were tested. No significant effect of VSC was observed for the melting behaviour of the ds-DNA sequence used. This demonstrates yet again the robustness of ds-DNA to outside perturbations. Our work also provides a general protocol to probe the effects of VSC on biological systems inside microfluid Fabry–Perot cavities and should be beneficial to better understand and harness this phenomenon.