Ice crystals can cause great damage. The utilization of antifreeze agents is an efficient method to prevent or reduce ice crystal formation and growth. Synthetic antifreeze agents are toxic and have low efficiency, and natural antifreeze proteins suffer from high cost and low stability. Here, we have designed and synthesized a series of peptoid oligomers by mimicking the antifreeze protein structure, and the structure-property relationship was also studied. The reported peptoids here have excellent antifreeze properties and are nontoxic to cells. These novel peptoid materials have great potential to replace current commonly used antifreeze agents, such as dimethyl sulfoxide, and become a new generation of antifreeze agents applied in cryopreservation.