Lipid nanoparticles (LNPs) have emerged as a promising platform for the delivery of various therapeutics. For long-term storage, LNPs are typically preserved at subzero temperatures with sugar-based stabilizers. In this study, we applied polymeric stabilizers as alternatives to commonly used sucrose. Experimental results showed that polymeric stabilizers provided superior stabilization compared to sucrose, suggesting their potential as effective alternatives for storage of LNPs. However, it remains unclear how stabilizers interact with membrane of LNP during freezing and thawing processes. To investigate mechanism and role of polymeric stabilizers during preservation, we performed molecular dynamics simulations of LNP in the presence of polymeric stabilizers under experimentally relevant conditions. The two polymeric stabilizers demonstrated distinct interaction behaviors with LNP, which may contribute to differences in their ability to prevent aggregation of LNPs during preservation.