Recent research on artificial cells shows promise for developing therapeutic delivery agents that mimic real cells. To be effective in vivo, these systems must survive in the circulatory system. This review discusses strategies inspired by red blood cells (RBCs) to enhance the viability of large, cell-like vehicles, particularly focusing on giant unilamellar vesicles (GUVs). RBCs are a simple model with long circulation times, making them ideal for biomimicry. The review highlights the key features of RBCs, such as size, shape, lipid composition, and osmotic balance, and how these can be replicated in GUVs. It also reviews various RBC-mimicking carriers, including GUVs, LUVs, and modified RBCs. The article emphasizes the importance of improving GUVs' stability and functionality for in vivo therapeutic applications. Despite their potential, GUVs face challenges in production and long-term survival. The review concludes that biomimicry of RBCs can significantly advance the development of therapeutic artificial cells.Recent research on artificial cells shows promise for developing therapeutic delivery agents that mimic real cells. To be effective in vivo, these systems must survive in the circulatory system. This review discusses strategies inspired by red blood cells (RBCs) to enhance the viability of large, cell-like vehicles, particularly focusing on giant unilamellar vesicles (GUVs). RBCs are a simple model with long circulation times, making them ideal for biomimicry. The review highlights the key features of RBCs, such as size, shape, lipid composition, and osmotic balance, and how these can be replicated in GUVs. It also reviews various RBC-mimicking carriers, including GUVs, LUVs, and modified RBCs. The article emphasizes the importance of improving GUVs' stability and functionality for in vivo therapeutic applications. Despite their potential, GUVs face challenges in production and long-term survival. The review concludes that biomimicry of RBCs can significantly advance the development of therapeutic artificial cells.