To develop solid lipid nanoparticles (SLNs) with stable lipid matrix structures for the delivery of bioactive compounds, a new class of SLNs was studied using propylene glycol monopalmitate (PGMP) and glyceryl monostearate (GMS) mixtures and carvacrol as a model lipophilic antimicrobial. Stable SLNs were fabricated at PGMP:GMS mass ratios of 2:1 and 1:1, and the carvacrol loading was up to 30% of lipids with >98% encapsulation efficiency and absence of visual instability. Fluorescence spectra and release profiles indicated the carvacrol was successfully encapsulated and homogeneously distributed within the SLNs. SLNs fabricated with equal masses of PGMP and GMS had better stability of carvacrol during storage and higher sphericity than those with a ratio of 2:1 and were much more effective than free carvacrol against Escherichia coli O157:H7 and Staphylococcus aureus. These findings demonstrated the potential applications of the studied SLNs in delivering lipophilic bioactive compounds in food and other products.