Lipid nanoparticles especially SLNs and NLCs are well trusted and long researched (almost 25 years) as a drug delivery platform in pharma for various biomedical applications. Literature has extensively discussed and recognized the role of excipient in formulation, stability, in vitro and in vivo effects of the lipid nanoparticles. Biocompatibility of lipid nanoparticles is highly dependent on nature and type of excipient used. The extensive use of wide ranged excipient in cosmetic and dermal application is reported, followed by average use in oral and pulmonary drug delivery. However, excipients administered via intravenous route are really limited and need to follow more strict guidelines on metal impurities, toxicity considerations beside their GRAS status.