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Mutual miscibility of soylecithin, tristearin, fatty acids (FAs), and curcumin was assessed by means of surface pressure–area isotherms at the air-solution interface in order to formulate modified solid lipid nanoparticles (SLN). Appearance of minima in the excess area (A ex) and changes in free energy of mixing (∆ G 0 ex) were recorded for systems with 20 mole% FAs. Modified SLNs, promising as topical drug delivery systems, were formulated using the lipids in combination with curcumin, stabilized by an aqueous Tween 60 solution. Optimal formulations were assessed by judiciously varying the FA chain length and composition. Physicochemical properties of SLNs were studied such as the size, zeta potential (by dynamic light scattering), morphology (by freeze fracture transmission electron microscopy), and thermal behavior (by differential scanning calorimetry). The size and zeta potential of the formulations were in the range 300–500 nm and–10 to–20 mV, respectively. Absorption and emission spectroscopic analyses supported the dynamic light scattering and differential scanning calorimetry data and confirmed localization of curcumin to the palisade layer of SLNs. These nanoparticles showed a sustained release of incorporated curcumin. Curcumin-loaded SLNs were effective against a gram-positive bacterial species, Bacillus amyloliquefaciens. Our results on the physicochemical properties of curcumin-loaded SLNs, the sustained release, and on antibacterial activity suggest that SLNs are promising delivery agents for topical drugs.