Background: Curcumin is a polyphenol natural product of the plant Curcuma longa. Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment. Purpose: We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model. Study Design: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice. Methods: The novel object recognition test was used to analyze the recognition memory function. The long-term potentiation was studied using electrophysiological analysis. Western blotting was used to assess the protein expression and activation status. Results: Recognition memory deficit began as early as 4 weeks of age in both male and female Tsc2+/− mice. Oral administration with SLCP activates AMPK activity and inhibits mTOR activity in the brain tissue of Tsc2+/− mice, and can rescue the electrophysiological abnormality and object recognition memory loss in the mice. Conclusions: Our results suggest that SLCP could be an effective treatment for TSC patients.