Low-density lipoproteins (LDL) make up the majority of the cholesterol found in the body, with hypercholesterolemia being a major cause of atherosclerosis. LDL receptors mediate endocytosis of LDL, diminishing the level of LDL in the blood plasma to homeostasis. After internalization, the ligand dissociates and the receptor folds back and recycles onto the cell surface, making itself available to bind to more LDL molecules. This activity is in part modulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), an inhibitory enzyme that binds with the EGF-A domain of the LDL receptor and prevents the conformational change of the receptor-ligand complex. This causes the natural intracellular degradation of the receptor, preventing recycling onto the cell surface. As a result, the cholesterol level increases in the blood stream causing hypercholesterolemia. Globally, about one third of heart diseases is caused by increased cholesterol level. Therefore, there is a need for a therapeutic approach that can inhibit PCSK9. Several peptides have already been identified that mimic the EFG-A domain of the LDL receptor and bind with PCSK9, inhibiting its action and allowing the receptor to perform its normal function. However, the delivery of a small peptide is difficult without a proper vehicle, since small peptides are rapidly cleared in the body. Our approach is to develop an injectable peptide-based hydrogel delivery system that incorporates a peptide inhibitor of PCSK9. This self-assembling peptide system is thixotropic and forms a hydrogel with high epitope presentation of the PCSK9 inhibitor. The result is a technology that has better targetability and persistence and can activate more receptors. The self-assembling peptide hydrogels were tested for their biocompatibility and immunogenicity through in vitro cell culture and in vivo subcutaneous injection in mice, respectively. The cholesterol lowering effect of the hydrogels was evaluated in an in vivo mouse model where they were fed a high cholesterol diet for 3 months, with monthly dosing of hydrogel and weekly bleeds to detect cholesterol level and IgG response. The goal of our work is to create a library of clinically relevant LDL lowering peptide hydrogel drugs that can be tailored for (i) decreased dosing, (ii) increased compliance, (iii) decreased immunogenicity compared to the standard-of-care monoclonal antibody Evolucimab® that would ensure long term utility of the therapeutic, and (iv) lower cost compared to the standard-of-care. Our rational design of the therapeutic platform may usher a new generation of LDL-lowering drugs on the market.