Using orbital angular momentum beams in a Michelson interferometer opens the possibility for non-invasive measurements of refractive index changes down to 10−6 refractive index units. We demonstrate the application of a twisted light interferometer to directly measure the concentration of NaCl and glucose solutions label-free and in situ and to monitor temperature differences in the mK-µK range. From these measurements we can extract a correlation of the refractive index to concentration and to temperature from a liquid sample which is in good agreement with literature. Applying this type of twisted light interferometry yields a novel, robust, and easily implementable method for in situ monitoring of concentration and temperature changes in microfluidic samples.