Lipopolysaccharide (LPS) has been implicated in increased gut permeability and low-grade mucosal inflammation, conditions that are linked to the pathophysiology of irritable bowel syndrome (IBS). Because increased dietary fat intake can both trigger IBS symptoms and promote LPS translocation in the gut, this study aimed to better understand how a turmeric formula (TF) affects fasting and postprandial LPS response, after a high-fat challenge in patients with IBS (primary outcome). Secondary outcomes included postprandial Apo-B48 and TAG as markers of chylomicron-mediated LPS translocation, as well as gastrointestinal (GI) symptoms and stool pattern. In this randomised, double-blind, placebo-controlled crossover trial, eighteen patients with IBS completed two high-fat challenge tests after 3-d supplementation with either 300 mg TF or placebo. Blood was collected in the fasting state and up to 5 h postprandially. Data were analysed using repeated-measures mixed models. TF did not significantly alter postprandial LPS levels compared with placebo but significantly reduced postprandial Apo-B48 and TAG (mean ratios 0·82 and 0·87, p = 0·04 and p = 0·01, respectively). Fasting LPS and TAG showed a non-significant reduction after TF (mean ratios 0·79 and 0·87; both p = 0·06, respectively). No differences were observed in GI symptoms or stool characteristics. To conclude, TF did not influence dietary fat-mediated LPS translocation, but it reduced postprandial chylomicron markers, indicating a potential attenuation of chylomicron-mediated postprandial inflammation. Together with the observed trend towards reduced fasting LPS levels, these findings suggest that TF might have beneficial effects on low-grade subclinical inflammation, which could be relevant for IBS patients.