This multicenter, prospective, randomized controlled trial (NCT03285152) evaluates the primary endpoint of feasibility of a very-low carbohydrate diet (VLCD) in 19 women with obesity/overweight and endometrial cancer, who are randomized 2:1 to either a VLCD or a standard diet for 21-28 days. Fifteen participants complete the study, with 91 ± 4% of VLCD meals consumed, 5.5 ± 0.8% weight lost, and no grade 3/4 adverse events. Secondary endpoints include assessments of tumor biology and circulating metabolic biomarkers. Fasting glucose and insulin fall 22 ± 5.9% and 60 ± 3.8%, while total cholesterol and low-density lipoprotein (LDL) rise 6 ± 2.7% and 17.8 ± 8.9%. In a pre-specified exploratory outcome, RNA-Seq shows enrichment of CD8 + T-cells (q < 0.034; NES > 1.75), confirmed by immunohistochemistry (IHC) showing CD8 + T-cells infiltration of the tumor margins (q = 0.034; NES = 1.75). We conclude that VLCD is feasible and well-tolerated.