Microfluidics and droplet-based assays are the basis for numerous high-throughput experiments, including bio-inspired microreactors and selection platforms for directed evolution. While elaborate techniques are available for the production of picoliter-sized droplets, there is an increasing demand for subsequent manipulation and control of the droplet interior. Here, we report on a straightforward method to rapidly adjust the size of single to several hundred double-emulsion droplets in a microfluidic sieve by varying the carrier fluid’s salt concentration. We show that the concomitant concentration changes in the droplet interior can drive a reversible demixing transition in a biomimetic binary fluid. As another application, we show that growing and shrinking of trapped droplets can be utilized to achieve a reversible dissociation of double-stranded DNA into single strands, i.e. cycles of reversible DNA hybridization, similar to PCR cycles, can be achieved by reversibly changing the droplet size at constant temperature. Altogether, our approach shows how a simple and temporally tunable manipulation of the size and the chemistry in prefabricated droplets can be achieved by an external control parameter.