Mucosal drug delivery is considered as a convenient, mild and safe route, especially for the treatment of chronic diseases. In general, mucosal routes include buccal, ocular, intranasal, pulmonary, vaginal and oral delivery. To increase the efficiency of mucosal delivery, nanocarriers have been extensively explored, of which lipidbased nanocarriers attract much attention due to their great biocompatibility, cell membrane affinity and other excellent physicochemical properties by using different kinds of lipids. However, the effectiveness of lipid-based nanocarriers is limited by numerous in vivo physiological barriers (e.g. chemical environment, mucus and epithelium) in tracts or cavities. Herein, modification strategies of these nanocarriers are widely investigated and show great improvement of drug bioavailability. The aim of this review is to introduce applications of lipid-based nanocarriers in different mucosal routes and discuss typical modification strategies.