Platelet transfusions are commonly used to restore hemostatic balance in patients with thrombocytopenia or active bleeding. Beyond their role in hemostasis, platelets are known to be involved in various pathological conditions. Therefore, platelets could be expanded as cell therapies for other diseases. Despite this potential, genetically modifying platelets is challenging due to (i) their lack of a nucleus, making conventional DNA-based transfection methods impractical and (ii) their natural tendency to become permanently active. Lipid nanoparticle (LNP) technology has emerged as a promising method for transfection due to its ability to efficiently deliver genetic material into cells. An ideal transfection agent for platelets would avoid activation while preserving their activation capacity when needed. However, not many attempts have been made to transfect platelets and a platelet-optimized mRNA-LNP formulation is currently absent. First, we screened various transfection agents using commercial lipid-based reagents. We found the best properties of platelet-modified LNPs that express the reporter protein, GFP, most effectively. Furthermore, we aimed to develop diverse LNP formulations using novel lipids through screening, targeting the most suitable LNP formulation for in vivo environments. We anticipate that further expansion of this technology could result in more effective platelet therapies for the management of various diseases influenced by platelets.