The new findings in the field of polymeric materials expanding their applications in improving the quality of health care are of primary concern. Undoubtedly, the alteration in surface properties of polymeric materials on addition of different additives may provide a step forward towards their better implications in many areas of science. In this regard, the interactions of poly(N-isopropylacrylamide) (PNIPAM) with two differently behaving additives may lead to a new method to carry the phase transition temperature of PNIPAM more near to body temperature so that it can be easily used in drug delivery through intravenous or oral insertion. Individually, the addition of sodium dodceylsulfate (SDS) and trimethylamine N-oxide (TMAO) is increasing and decreasing the lower critical solution temperature (LCST) of PNIPAM as compared to classical LCST of PNIPAM in aqueous solution, respectively. In the present study, we try to emphasis the role of mixed SDS and TMAO environment in varying ratios on the phase transition behaviour of PNIPAM. Many biophysical techniques are employed such as UV-visible spectroscopy, fluorescence spectroscopy and dynamic light scattering (DLS), Laser Raman spectroscopy technique and Field emission scanning electron Microscopy (FESEM) for this part of work. The SDS is observed to form globules with PNIPAM segments and do not lead to turbidity of solution for the concentration greater than 10 µM. The negatively charged SDS bound PNIPAM globules that do not allow PNIPAM to associate, however; TMAO leads to turbid solution resulted from the hydrophobic association of PNIPAM. SDS is found to be very effective in increasing the LCST up to 62.8 °C even at very low (7.5 mM) concentration as compared to decreasing efficiency of TMAO where LCST reaches up to 29.4 °C for 0.75 M however, their mixture in specified concentration (1 mM SDS and 0.1 M TMAO) can bring the LCST of PNIPAM very near to body temperature (i.e. ∼36 °C) that is quiet promising for its use in target delivery engineering. TMAO ability to counteract the adverse effect of SDS is the main core reason in getting LCST near to body temperature. Copyright © 2018 Elsevier Inc. All rights reserved.