Solid lipid nanoparticles (SLNs) are promising drug delivery vehicles for the delivery of various drugs, especially poorly water-soluble drugs. However, the aqueous stability, drug release, and biocompatibility of SLNs are some of the issues that need attention. In this work, curcumin-loaded SLNs were prepared, and morphology, particle size, and entrapment efficiency were studied. For this, two amino acid-derived lipids were developed. The effect of the polarity of the lipid head on the aqueous stability of the SLN dispersion was investigated. Based on the stability, particle size, and polydispersity, an optimum formulation was obtained. The curcumin entrapment efficiency of the SLNs was found to be greater than those reported in the literature. The entrapped curcumin, as well as curcumin-loaded SLN suspensions, exhibited improved storage stability. The in vitro release kinetics indicated an enhanced rate of drug release in the case of curcumin-loaded SLNs consisting of the lipid containing -OH groups at the lipid head. The pure lipid and the blank SLN were found to have no significant cytotoxicity, but curcumin and curcumin-loaded SLNs induced cell death in a concentration-dependent manner in both human prostatic adenocarcinoma PC3 cell line and human breast carcinoma MCF7 cell line. This study has proposed a potential semisynthetic lipid for the stable SLN suspension for the delivery of curcumin.