A new class of cationic polymers containing tertiary amine, thioether, and hydroxyl groups are prepared via a catalyst‐free, multicomponent polymerization method using dithiol, formaldehyde, and di‐sec‐amine with a ratio of 1:2:1, to access a library of water‐soluble polymers with well‐defined structures and suitable molecular weights (Mw ranging from 5000 to 8000 Da) in high yields (up to 90%). Such polycations are demonstrated to be promising nonviral gene delivery vectors with high transfection efficiency (up to 3.5‐fold of PEI25k) and low toxicity with multiple functionalities: 1) efficient gene condensation by tertiary amine groups; 2) reactive oxygen species scavenging by thioether groups; and 3) positive charge shielding by hydroxyl groups. Both the thioether and hydroxyl groups are contributed to reduce the cytotoxicity of the polycations by tuning the oxidative stress and preventing the undesired serum binding. The optimized polycations can achieve high transfection efficiency under the serum conditions, indicating the great potential as a nonviral gene delivery vector candidate for clinical application.