Introduction Obesity is a major health concern in postmenopausal women, and chronic low-grade inflammation contributes to the development of obesity. Cellular studies and high-fat-diet-induced obese mouse model mimicking obesity show the antiobesity effect of annatto-extracted tocotrienols (TT) with antioxidant capability. We aim to assess the safety and efficacy of TT consumption for lipid-related parameters in obese postmenopausal women. Methods and analysis Eligible obese postmenopausal women will be randomly assigned to placebo group (430 mg olive oil) and TT group (DeltaGold Tocotrienol 70%) for 24 weeks. In the present study, the primary outcome is total/regional fat mass and visceral adipose tissue. The secondary outcomes include lipid profile in serum, mRNA expression of fatty acid synthase and carnitine palmitoyltransferase 1A in fat tissue, oxylipins and endocannabinoids in plasma and adipose tissue, abundance and composition of intestinal microbiome in faeces, high-sensitivity C-reactive protein (hs-CRP) in serum and leptin in serum. Every participant will be evaluated at 0 (prior to starting intervention) and 24 weeks of intervention, except for serum lipid profile and hs-CRP at 0, 12 and 24 weeks. â € Intent-to-treat' principle is employed for data analysis. Hierarchical linear modelling is used to estimate the effects of dietary TT supplementation while properly accounting for dependency of data and identified covariates. To our knowledge, this is the first randomised, placebo-controlled, double-blinded study to determine dietary TT supplementation on an obese population. If successful, this study will guide the future efficacy TT interventions and TT can be implemented as an alternative for obese population in antiobesity management. Ethics and dissemination This study has been approved by the Bioethics Committee of the Texas Tech University Health Sciences Center, Lubbock. An informed consent form will be signed by a participant before enrolling in the study. The results from this trial will be actively disseminated through academic conference presentation and peer-reviewed journals. Trial registration number NCT03705845.