Lipid-based nanoparticles hold great potential for drug delivery, providing biocompatibility and the ability to encapsulate both hydrophilic and hydrophobic drugs. However, there are certain challenges associated with small molecules, such as leakage and premature release, which can compromise their effectiveness. Despite these challenges, lipid nanoparticles offer advantages in terms of solubility, stability, and targeted delivery, thereby reducing side effects. Additionally, they can be customized for specific molecules, ensuring biocompatibility and biodegradability. While complications may arise, lipid nanoparticles offer numerous benefits for loading biomolecules, improving pharmacokinetics, and enhancing therapeutic effects. It is important to address stability and loading challenges when encapsulating biomolecules and consider potential immunogenic responses that may impact biocompatibility and safety.