Palanivel Ganesan,1,2,* Prakash Ramalingam,3,4,* Govindarajan Karthivashan,1,* Young Tag Ko,4 Dong-Kug Choi1,2 1Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Republic of Korea; 2Nanotechnology Research Center and Department of Applied Life Science, Konkuk University, Chungju, Republic of Korea; 3Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA; 4College of Pharmacy, Gachon University, Incheon, Republic of Korea *These authors contributed equally to this work Abstract: Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. Keywords: solid lipid nanoparticles, surface-modified solid lipid nanoparticles, chronic diseases, phyto-bioactive compounds, chitosan