Curcumin is a polyphenol compound widely investigated for its potential health benefits. Clinical evidence from randomized controlled trials shows substantial positive effects in healthy individuals but contrasting results for patients with cardio-metabolic disorders. There is growing evidence that the gut microbiota may play a role in curcumin transformation and absorption of more bioactive compounds, suggesting that the baseline health status (or other unmeasured variables) may explain the observed variability of the results.