PurposeThis randomized controlled parallel-group study examined the effects of a very low-carbohydrate high-fat (VLCHF) diet and high-intensity interval training (HIIT) program over 12-weeks on cardiometabolic risk factors in individuals with overfat constitution.MethodsNinety-one participants out of 109 completed the study. The participants were randomly allocated to the HIIT (N = 22), VLCHF (N = 25), VLCHF+HIIT (N = 25), or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4 and 12 weeks. The analyzed outcomes included complete blood count, glucose, insulin, glycated hemoglobin, triglycerides (TG), cholesterol, high- and low-density lipoprotein (HDL-C and LDL-C), lipoprotein(a), adiponectin (Adpn), leptin (Lep), tumor necrosis factor α (TNF-α), other interleukins (hs-IL-6, IL-1β, and IL-10), and IL-1RA. The homeostasis model assessment of insulin resistance (HOMA-IR), Adpn/Lep ratio, TG/HDL-C ratio, and TyG index were calculated and analyzed. Blood pressure was measured before the intervention, after 4, 8, and 12 weeks (ClinicalTrials.gov: NCT03934476).ResultsAbsolute changes in HOMA-IR, Adpn/Lep ratio, LDL-C, and diastolic blood pressure after 12 weeks differed by study groups (p < 0.05). The most pronounced changes were revealed in the VLCHF (ΔM [95% CI]; HOMA-IR: −0.75 [−1.13; −0.55]; Adpn/Lep: 9.34 [6.33; 37.39]; LDL-C: 0.06 [−0.12; 0.50] mmol/l) and VLCHF+HIIT (HOMA-IR: −0.44 [−1.14; 0.12]; Adpn/Lep: 4.26 [2.24; 13.16]; LDL-C: 0.25 [−0.04; 0.50] mmol/l) groups.ConclusionsA 12-week VLCHF diet intervention in individuals with overfat constitution is effective for favorable changes in HOMA-IR (compared to HIIT), Adpn/Lep ratio, and diastolic blood pressure. HIIT, or HIIT combined with the VLCHF diet, had no additional benefits for the analyzed variables. No adverse side effects were observed.