The beguiling world of functional polymers is dominated by thermoresponsive polymers with unique structural and molecular attributes. Limited work has been reported on the protein-induced conformational transition of block copolymers; furthermore, the literature lacks a clear understanding of the influence of proteins on the phase behavior of thermoresponsive copolymers. Herein, we have synthesized poly(N-isopropylacrylamide)-b-poly(N-vinylcaprolactam) (PNIPAM-b-PNVCL) by RAFT polymerization using N-isopropylacrylamide and N-vinylcaprolactam. Furthermore, using various biophysical techniques, we have explored the effect of cytochrome c (Cyt c), myoglobin (Mb), and hemoglobin (Hb) with varying concentrations on the aggregation behavior of PNIPAM-b-PNVCL. Absorption and steady-state fluorescence spectroscopy measurements were performed at room temperature to examine the copolymerization effect on fluorescent probe binding and biomolecular interactions between PNIPAM-b-PNVCL and proteins. Furthermore, temperature-dependent fluorescence spectroscopy and dynamic light scattering studies were performed to get deeper insights into the lower critical solution temperature (LCST) of PNIPAM-b-PNVCL. Small-angle neutron scattering (SANS) was also employed to understand the copolymer behavior in the presence of heme proteins. With the incorporation of proteins to PNIPAM-b-PNVCL aqueous solution, LCST has been varied to different extents owing to the preferential, molecular, and noncovalent interactions between PNIPAM-b-PNVCL and proteins. The present study can pave new insights between heme proteins and block copolymer interactions, which will help design biomimetic surfaces and aid in the strategic fabrication of copolymer-protein bioconjugates.