Protein-polymer conjugates improve therapeutic efficacy of proteins and have been widely used for the treatment of various diseases such as cancer, diabetes, and hepatitis. PEGylation is considered as the “gold standard” in bioconjugation, although in practice its clinical applications are becoming limited because of extensive evidence of immunogenicity induced by pre-existing anti-PEG antibodies in patients. PEG immunogenicity leads to loss of protein activity, reduced safety, and accelerated clearance of the therapeutics. Advancements in polymerization techniques and bioconjugation chemistries have allowed for the development of well-defined conjugates that can circumvent these adverse effects while retaining the benefits of such modifications. Development of controlled polymerization techniques like atom transfer radical polymerization (ATRP), reversible addition-fragmentation polymerization (RAFT), nitroxide mediated polymerization (NMP), and ring-opening metathesis polymerization (ROMP) have enabled the synthesis of well-defined multifunctional systems with low dispersity (Ð), a variety of end-group functionalities, and architectures. Our lab has been studying synthesis of protein-polymer conjugates using ROMP technique. ROMP is fast and extremely functional group tolerant which allows for the design of diverse functional polymers. In this dissertation, we show the synthesis of ROMP-derived polynorbornene based-protein conjugates by both grafting-from and grafting-to conjugation. We studied the effect of polynorbornene conjugation on protein activity, stability, and immunogenicity. Additionally, we study the reactivity of anti-PEG antibodies with polynorbornene-protein conjugates. We also compare the conjugates with PEGylated version of proteins to show the effectiveness of conjugates developed in our studies.