Amphiphilic homopolymers with high densities of functional groups are synthetically challenging. Thiol-yne nucleophilic click reactions have been investigated to introduce multiple functional groups in polymers with high density. An electron deficient alkyne group bearing methacrylate monomer was polymerized using reversible addition−fragmentation chain-transfer (RAFT) polymerization. Subsequently, the electron deficient alkyne group on polymer side chain was readily reacted with a thiol reagent using triethylamine (TEA) as the organocatalyst. This reaction was found to be very efficient under mild conditions. The resultant homopolymer bearing thiol vinyl ether functional groups could perform a second thiol addition with a stronger base, such as triazabicyclodecene(TBD), to prepare multifunctional homopolymers. This stepwise addition process was monitored by different techniques. The fidelity of this method was demonstrated by attaching four different functionalities, including both hydrophobic and hydrophilic moieties. Also, a novel polymerization method was developed using the same thiol-yne nucleophilic addition strategy. Typically, two bi-functional thiol-based monomers with activated alkyne termini differencing in their linker length can be prepared and polymerized utilizing this strategy. Under mild conditions, monomers can be polymerized conveniently to yield linear structures with high molecular weights. The polymerization conditions were optimized by screening various catalysts, solvents, temperatures, reaction time, and monomer concentrations. This new methodology efficiently yields polymers with high molecular weight. Moreover, the resulting polymer contains alkene backbone that acts as a functional handle for further modifications. For example, it can be subjected to a second thiol species to achieve multi-functional capabilities. These post-modified polymers with dithioacetal units in their backbone degrade in the presence of reactive oxygen species, providing the opportunity to design functional materials with stimuli-responsive features.