Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following interactions with organelles and macromolecules can result in negative effects on cells, especially, they can induce cytotoxicity, epigenicity, genotoxicity, and cell death. Lipid-based nanomaterials (LNPs) are one of the most important achievements in drug delivery mainly due to their superior physicochemical and biological characteristics, particularly its safety. Although they are considered as the completely safe nanocarriers in biomedicine, the lipid composition, the surfactant, emulsifier, and stabilizer used in the LNP preparation, and surface electrical charge are important factors that might influence the toxicity of LNPs. According to the author's opinion, their toxicity profile should be evaluated case-by-case regarding the intended applications. Since there is a lack of all-inclusive review on the various aspects of LNPs with an emphasis on toxicological profiles including cyto-genotoxiciy, this comprehensive and critical review is outlined.