Curcumin-loaded solid lipid nanoparticles (Cur-SLN) were prepared using medium- and long chain diacylglycerol (MLCD) or glycerol tripalmitate (TP) as lipid matrix and three kinds of surfactants including Tween 20 (T20), quillaja saponin (SQ) and rhamnolipid (Rha). The MLCD-based SLNs had a smaller size and lower surface charge than TP-SLNs with a Cur encapsulation efficiency of 87.54–95.32% and the Rha-based SLNs exhibited a small size but low stability to pH decreases and ionic strength. Thermal analysis and X-ray diffraction results confirmed that the SLNs with different lipid cores showed varying structures, melting and crystallization profiles. The emulsifiers slightly impacted the crystal polymorphism of MLCD-SLNs but largely influenced that of TP-SLNs. Meanwhile, the polymorphism transition was less significant for MLCD-SLNs, which accounted for the better stabilization of particle size and higher encapsulation efficiency of MLCD-SLNs during storage. In vitro studies showed that emulsifier formulation greatly impacted on the Cur bioavailability, whereby T20-SLNs showed much higher digestibility and bioavailability than that of SQ- and Rha-SLNs possibly due to the difference in the interfacial composition. Mathematical modeling analysis of the membrane release further confirmed that Cur was mainly released from the intestinal phase and T20-SLNs showed a faster release rate compared with other formulations. This work contributes to a better understanding of the performance of MLCD in lipophilic compound-loaded SLNs and has important implications for the rational design of lipid nanocarriers and in instructing their application in functional food products.