Background: MGUS (Monoclonal Gammopathy of Undetermined Significance) and Smoldering Multiple Myeloma (SMM) represent useful models for studying multiple myeloma precursor disease, and for developing early intervention strategies. Trial design: Administering a 4g dose of curcumin, we performed a randomised, double-blind placebo-controlled cross-over study, followed by an open-label extension study using an 8g dose to assess the effect of curcumin on markers of disease progression and bone turnover in patients with MGUS and SMM. Methods: Thirty six patients (19 MGUS and 17 SMM) were randomised into two groups: one received 4g curcumin or 4g placebo, crossing over at 3 months. At completion of the 4g arm, all patients were given the option of entering an open-label, 8g dose extension study. Blood and urine samples were collected at specified intervals for specific marker analyses. Group values are expressed as mean + 1 SD. Data from different time intervals within groups were compared using Student’s paired t-test. Results: Twenty-five patients completed the 4g cross-over study and 18 the 8g extension study. Curcumin therapy decreased the free light-chain ratio (rFLC) and reduced the difference between clonal and nonclonal light-chain (dFLC). uDPYD, a marker of bone resorption, decreased in the curcumin arm (-9% to -22%) and increased on the placebo arm. Serum creatinine levels tended to diminish on curcumin therapy. Conclusion: These findings suggest that curcumin might have the potential to slow the disease process in patients with MGUS and SMM.